SEC62

Chr 3

SEC62 preprotein translocation factor

Also known as: Dtrp1, HTP1, TLOC1, TP-1

NCBI Gene: 7095 ENSG00000008952 UniProt: Q99442

The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. The protein encoded by this gene and SEC63 protein are found to be associated with ribosome-free SEC61 complex. It is speculated that Sec61-Sec62-Sec63 may perform post-translational protein translocation into the ER. The Sec61-Sec62-Sec63 complex might also perform the backward transport of ER proteins that are subject to the ubiquitin-proteasome-dependent degradation pathway. The encoded protein is an integral membrane protein located in the rough ER. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Clinical highlights

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.983

Z-score 3.87

OE 0.09 (0.04–0.30)

Highly constrained

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

Missense Constraint?

1.78Z-score

OE missense 0.65 (0.56–0.75)

130 obs / 201.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.30)

0≤0.351.4

Missense OE?0.65 (0.56–0.75)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 2 / 21.2Missense obs/exp: 130 / 201.2Syn Z: 0.07

Background carrier burden — how many people carry a rare variant somewhere in SEC62?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

355 rare PASS variants

Rare truncating (LoF)

1 in 1,600

28 rare PASS variants

Rare synonymous (reference)

1 in 370

147 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SEC62. 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 280	1 in 1,800
South Asian	~43k	1 in 240	1 in 890
Remaining (unassigned)	~30k	1 in 260	1 in 2,200
European (Finnish)	~27k	1 in 320	1 in 1,600
Admixed American	~22k	1 in 200	1 in 550
African / African American	~21k	1 in 270	1 in 2,500
East Asian	~20k	1 in 200	1 in 950
Ashkenazi Jewish	~13k	1 in 380	1 in 2,300
Middle Eastern	~2,884	1 in 240	≈ 1 in 950

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): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓