HAPSTR1

Chr 16

HUWE1 associated protein modifying stress responses

Also known as: C16orf72, PRO0149, TAPR1

NCBI Gene: 29035 ENSG00000182831 UniProt: Q14CZ0 OMIM: 621638

HAPSTR1 encodes a protein that negatively regulates p53-mediated stress response pathways and cellular responses to telomere erosion and DNA damage through interactions with the E3 ubiquitin ligase HUWE1. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.29), but no human diseases have been definitively associated with HAPSTR1 mutations to date. Given its critical role in DNA damage response and high constraint scores, pathogenic variants would likely cause severe developmental or neurological phenotypes.

OMIM ResearchSummary from RefSeq, UniProt

Enables ubiquitin protein ligase binding activity. Involved in negative regulation of signal transduction by p53 class mediator and regulation of cellular response to stress. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.29

Clinical Summary— HAPSTR1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

7 total variants — no pathogenic classifications of 7 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.980

Z-score 3.53

OE 0.06 (0.02–0.29)

Highly constrained

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

Missense Constraint?

1.95Z-score

OE missense 0.56 (0.47–0.67)

87 obs / 155.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.29)

0≤0.351.4

Missense OE?0.56 (0.47–0.67)

0≤0.61.4

Synonymous OE?1.62

0≤1.21.6

LoF obs/exp: 1 / 16.4Missense obs/exp: 87 / 155.3Syn Z: -3.70

ClinVar Variant Classifications

7 submitted variants in ClinVar

ClinVar

Classification Summary

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

Classification	LoF	Missense + Inframe	Non-coding	Synonymous
Pathogenic	—	—	—	—
Likely Pathogenic	—	—	—	—
VUS	—	—	—	—
Likely Benign	—	—	—	—
Benign	—	—	—	—
Total	—

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

24 pathogenic / likely-pathogenic (of 54) ClinVar copy-number / structural variants overlap HAPSTR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →