SEC11A

Chr 15

SEC11 homolog A, signal peptidase complex subunit

Also known as: 1810012E07Rik, SEC11L1, SPC18, SPCS4A, sid2895

NCBI Gene: 23478 ENSG00000140612 UniProt: P67812 OMIM: 618258

The protein is a catalytic component of the signal peptidase complex that cleaves N-terminal signal sequences from nascent proteins as they are translocated into the endoplasmic reticulum. Mutations cause autosomal recessive congenital disorder of glycosylation with severe developmental delay, seizures, and multisystem involvement. The gene shows low constraint to loss-of-function variation, consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the peptidase S26B family. The encoded protein is an 18kDa subunit of the signal peptidase complex and has been linked to cell migration and invasion, gastric cancer and lymph node metastasis. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 8. [provided by RefSeq, Dec 2012]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.99

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.002

Z-score 1.59

OE 0.50 (0.28–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.58Z-score

OE missense 0.55 (0.44–0.69)

53 obs / 96.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.28–0.99)

0≤0.351.4

Missense OE?0.55 (0.44–0.69)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 6 / 11.9Missense obs/exp: 53 / 96.8Syn Z: 0.44

Background carrier burden — how many people carry a rare variant somewhere in SEC11A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 350

228 rare PASS variants

Rare truncating (LoF)

1 in 5,500

49 rare PASS variants

Rare synonymous (reference)

1 in 760

89 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SEC11A. 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 460	1 in 5,500
South Asian	~43k	1 in 350	1 in 5,100
Remaining (unassigned)	~30k	1 in 250	≈ 1 in 14,000
European (Finnish)	~27k	1 in 3,800	≈ 1 in 8,900
Admixed American	~22k	1 in 560	none seen
African / African American	~21k	1 in 610	1 in 2,500
East Asian	~20k	1 in 440	1 in 3,900
Ashkenazi Jewish	~13k	1 in 540	none seen
Middle Eastern	~2,883	1 in 410	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.

Exome coverage (gnomAD): 4 of 6 coding exons well covered in gnomAD exomes; exon 5 poorly covered; exon 2 marginal. Genomes: all 6.? see exons ↓