The first disease pinned to a protein spelling
Sickle cell disease was the first human disease understood as a change in a protein. In the 1940s and 1950s, Linus Pauling and Vernon Ingram showed that hemoglobin S differs from normal hemoglobin by one amino acid. That amino acid is encoded by one letter in the HBB gene. The public name of the site is rs334.
If you inherit the sickle allele from both parents, red blood cells can deform under stress. If you inherit it from one parent, you have sickle cell trait, which is usually milder and in some regions historically associated with malaria resistance. Those are clinical categories. An rsID lookup is not a hemoglobin electrophoresis.
The story is famous because it is simple: one gene, one letter, a visible protein change. Most human traits are not simple. Use rs334 as a clean example. Do not treat every SNP in a spit kit as if it were sickle cell.
- HBB: the beta-globin gene on chromosome 11
- rs334: the public id for the Glu6Val sickle allele
- Trait vs disease: one copy versus two, in clinical context
rs334 sickle cell is the HBB Glu6Val public record
rs334 sickle cell refers to the dbSNP cluster at the HBB sickle allele, classically written Glu6Val (HbS). Some HGVS protein strings count the initiator methionine and write p.Glu7Val. Confirm on dbSNP or ClinVar instead of memorizing one number.
The site sits in HBB on chromosome 11. ClinVar submissions for the sickle allele are among the most cited examples in tutorials, including genome.sh’s homepage demo.
That makes rs334 a good identifier to test a CLI. It does not make a chip lookup a sickle cell test. Hemoglobinopathies are diagnosed with clinical assays.
If you only remember one mapping, remember rs334 to HBB Glu6Val. Confirm the live dbSNP page when the protein numbering in a paper disagrees. Do not let a Glu6 versus Glu7 argument block a CLI test of a public id.
- rs334: dbSNP cluster for the HBB sickle allele
- Legacy protein: Glu6Val / HbS
- Clinical testing: hemoglobin assays, not a dbSNP lookup
Why tutorials and the homepage use this rsID
The record is public, well documented, and exercises ClinVar fields. No personal data is required to query it. That is why demos start here instead of a random VUS.
You can query the rsID, then the gene HBB, then JSON, and see significance next to frequency. The lesson is the lookup path, not a diagnosis.
If you are writing a pipeline, keep rs334 as a fixture. If you are reading a personal file, apply the same not-called rule you would for any other site.
Use it as a smoke test after install. If genome query rs334 fails, the database is not installed. If it succeeds, you still have not tested a person. You tested the lookup path.
Query rs334, then HBB, then JSON
Install genome-sh and a database tier. genome query rs334 is the site. genome query HBB is the gene catalog. They are different objects.
Human output is for one terminal. --format json is for jq. --format compact is the short form. The HTTP API mirrors the identifier lookup without a key.
Do not POST a VCF. Annotate locally if you have a file.
cargo install genome-sh genome db install lite genome query rs334 genome query rs334 --format json | jq . genome query HBB --format json | jq 'length' curl -s https://api.genome.sh/v1/query/rs334 | jq .
ClinVar coverage is strong; a chip is still not an assay
rs334 is a rare case where the public clinical record is famous. Review status still matters. Read the stars and the conditions, not only the word Pathogenic.
Zygosity matters in real care. Heterozygous sickle trait and homozygous sickle disease are different clinical objects. A CLI does not know which one a person has until a file is called, and even then a chip is not a hemoglobin electrophoresis.
If the chip did not call rs334, write not called. Missing is not wild type. Often-on-the-array is not always-on-the-array.
Other HBB alleles such as HbC are different rsIDs and often different assays. Querying rs334 does not test the rest of HBB. genome query HBB is a catalog, not a panel result.
Allele frequency and population context
gnomAD frequencies for rs334 vary by ancestry group. A global AF can hide a higher frequency in one group. That is population genetics, not a personal result.
Frequency does not delete ClinVar. ClinVar does not delete frequency. Read both. Install standard or full if you want gnomAD in the same JSON object.
Malaria-related selection is a textbook story around this allele. genome.sh will not teach that story as a diagnosis engine. It will print AF when the snapshot has it.
When you publish a tutorial, keep rs334 in the fixture list next to rs1799945. Both are public. Neither should be replaced with a real sample genotype in a blog post.
genome db install standard
genome query rs334 --format json | jq '{clinvar, gnomad}'
curl -s https://api.genome.sh/v1/gnomad/rs334 | jq .Match the rsID to a local file
grep the rsID in a 23andMe-style export or annotate a VCF. genome annotate file.vcf.gz --format json is the local job.
A called genotype is two letters plus a public annotation. It is still not a sickle cell screen for other HBB variants. HbC and beta-thalassemia alleles are different rsIDs and often different assays.
Keep the file on disk. Do not paste it into a chatbot because you wanted to know what rs334 means.
If you convert a consumer export to VCF first, you still only have chip sites. genome annotate will not summon electrophoresis. Keep the not-called language in any PDF.
- Site lookup: genome query rs334
- Gene catalog: genome query HBB
- File match: grep or genome annotate, missing = not called
Clinical hemoglobin testing is separate
Newborn screening, HPLC, electrophoresis, and clinical sequencing are how hemoglobinopathies are diagnosed. A dbSNP lookup is none of those.
genome.sh prints public annotations. It is not a medical device. Point people who need care to a clinician.
Use rs334 as the worked example it is. Then query the identifiers you actually have.
JSON fields worth keeping for a tutorial fixture
For a pipeline test, assert that rs334 returns a ClinVar significance and a review status. Do not assert a specific star count in CI if your snapshot can move. Assert that the rsID resolved.
Add a gnomAD assertion only on standard or full. lite is allowed to omit frequency. Check genome db stats in the same test so a lite install does not look like a missing allele.
The homepage uses this rsID because it is public. Your personal file is not public. Query the identifier over HTTPS if you want. Match the genotype on disk.
genome query rs334 --format json | jq '{rsid, significance, review_status, gnomad}'
curl -s https://api.genome.sh/v1/query/HBB | jq '.[0:3]'
genome db statsQuestions
What is rs334 sickle cell?
rs334 is the dbSNP id for the HBB sickle allele, classically Glu6Val. Some protein strings write p.Glu7Val because they count the initiator methionine. Confirm on dbSNP. It is a public record, not a hemoglobinopathy diagnosis.
Is rs334 always called on 23andMe?
Often, not always. Check the file. Missing is not called, not wild type.
Can I query HBB instead of rs334?
Yes. genome query HBB returns variants for the gene, not one site. Use it after the rsID if you want the catalog.
Why does the genome.sh homepage use rs334?
It is public, well documented, and exercises ClinVar fields. No personal data is involved.
How do I look up rs334 from the command line?
cargo install genome-sh, genome db install lite, then genome query rs334. Add --format json | jq . for scripts.
Does heterozygous rs334 mean sickle cell disease?
genome.sh will not diagnose. Trait and disease are clinical objects that use zygosity, other HBB alleles, and laboratory assays. A chip lookup of rs334 is not hemoglobin electrophoresis.
Is Glu6Val the same as p.Glu7Val?
They can name the same HbS change with different methionine counting. Confirm on the dbSNP or ClinVar page for rs334.
Is this medical advice?
No. Clinical hemoglobin testing belongs in a clinical lab.