HM13

Chr 20

histocompatibility minor 13

Also known as: H13, HM13-IT1, IMP1, IMPAS, IMPAS-1, MSTP086, PSENL3, PSL3

This endoplasmic reticulum-localized aspartic protease catalyzes intramembrane proteolysis of signal peptides after their cleavage from precursor proteins, generates HLA-E epitopes for immune recognition, and processes hepatitis C virus core protein. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.43), indicating intolerance to complete protein loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
10
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
0.43
LOEUF
Mechanism
Clinical SummaryHM13
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.69) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 50 VUS of 93 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.43LOEUF
pLI 0.690
Z-score 3.48
OE 0.19 (0.090.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.09Z-score
OE missense 0.62 (0.540.71)
151 obs / 242.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.19 (0.090.43)
00.351.4
Missense OE0.62 (0.540.71)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 4 / 21.3Missense obs/exp: 151 / 242.9Syn Z: 1.38

ClinVar Variant Classifications

93 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic6
VUS50
Likely Benign6
10
Pathogenic
6
Likely Pathogenic
50
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
6
0
6
VUS
0
42
8
0
50
Likely Benign
0
0
6
0
6
Benign
0
0
0
0
0
Total04230072

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

View in ClinVar →

Protein Context — Lollipop Plot

HM13 · 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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