SEC61A1

Chr 3AD

SEC61 translocon subunit alpha 1

Also known as: ADTKD5, CVID15, HNFJ4, HSEC61, SEC61, SEC61A

NCBI Gene: 29927 ENSG00000058262 UniProt: P61619 OMIM: 609213

The protein encoded by this gene belongs to the SECY/SEC61- alpha family. It appears to play a crucial role in the insertion of secretory and membrane polypeptides into the endoplasmic reticulum. This protein found to be tightly associated with membrane-bound ribosomes, either directly or through adaptor proteins. This gene encodes an alpha subunit of the heteromeric SEC61 complex, which also contains beta and gamma subunits. [provided by RefSeq, Jul 2008]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Neutropenia, severe congenital, 11, autosomal dominantMIM #620674

Immunodeficiency, common variable, 15MIM #620670

Tubulointerstitial kidney disease, autosomal dominant, 5MIM #617056

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · SEC61A1 deficiency · AD · ClinGen 2021

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — SEC61A1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.29LOEUF

pLI 0.987

Z-score 4.21

OE 0.11 (0.05–0.29)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

4.06Z-score

OE missense 0.32 (0.27–0.38)

92 obs / 284.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.11 (0.05–0.29)

0≤0.351.4

Missense OE?0.32 (0.27–0.38)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 3 / 26.3Missense obs/exp: 92 / 284.9Syn Z: -0.30

Background carrier burden — how many people carry a rare variant somewhere in SEC61A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 550

309 rare PASS variants

Rare truncating (LoF)

1 in 6,800

43 rare PASS variants

Rare synonymous (reference)

1 in 100

267 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SEC61A1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 670	1 in 7,200
South Asian	~43k	1 in 340	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 490	1 in 980
European (Finnish)	~27k	1 in 1,400	≈ 1 in 27,000
Admixed American	~22k	1 in 580	≈ 1 in 7,300
African / African American	~21k	1 in 380	≈ 1 in 4,600
East Asian	~20k	1 in 390	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 1,400	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 580	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.