SECTM1

Chr 17

secreted and transmembrane 1

Also known as: K12, SECTM

The protein is a transmembrane protein involved in thymocyte signaling and hematopoietic/immune system processes. Mutations in this gene have not been established to cause pediatric neurological disease. The predicted gain-of-function mechanism and tolerance to loss-of-function mutations (high LOEUF score) suggest this gene may not be associated with haploinsufficiency disorders.

Summary from RefSeq, UniProt, Mechanism
0
Active trials
7
Pubs (1 yr)
22
P/LP submissions
0%
P/LP missense
1.03
LOEUF
GOF
Mechanism· predicted
Clinical SummarySECTM1
Population Constraint (gnomAD)
Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 46 VUS of 83 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.058
Z-score 1.52
OE 0.40 (0.181.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.35Z-score
OE missense 0.92 (0.801.06)
139 obs / 151.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.40 (0.181.03)
00.351.4
Missense OE0.92 (0.801.06)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 3 / 7.5Missense obs/exp: 139 / 151.1Syn Z: -1.16
DN
0.6938th %ile
GOF
0.73top 25%
LOF
0.2190th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

83 submitted variants in ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic3
VUS46
Likely Benign8
19
Pathogenic
3
Likely Pathogenic
46
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
3
0
3
VUS
0
35
11
0
46
Likely Benign
0
6
1
1
8
Benign
0
0
0
0
0
Total04134176

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SECTM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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