HIRIP3

Chr 16

HIRA interacting protein 3

NCBI Gene: 8479ENSG00000149929UniProt: Q9BW71OMIM: 603365

HIRIP3 encodes a histone chaperone that facilitates the deposition of H2A-H2B histone complexes onto chromatin and functions as part of a multiprotein complex involved in chromatin and histone metabolism. Mutations in HIRIP3 cause neurodevelopmental disorder with seizures, hypotonia, and delayed development, which follows an autosomal recessive inheritance pattern. This chromatin remodeling disorder typically presents in early infancy with developmental delays and neurological manifestations.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.87
Clinical Summary— HIRIP3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
278 unique Pathogenic / Likely Pathogenic· 99 VUS of 401 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.000
Z-score 2.06
OE 0.55 (0.35–0.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.82Z-score
OE missense 1.13 (1.03–1.23)
366 obs / 324.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.55 (0.35–0.87)
0≤0.351.4
Missense OE1.13 (1.03–1.23)
0≤0.61.4
Synonymous OE1.11
0≤1.21.6
LoF obs/exp: 13 / 23.8Missense obs/exp: 366 / 324.4Syn Z: -0.93

ClinVar Variant Classifications

401 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic234
Likely Pathogenic44
VUS99
Likely Benign4
234
Pathogenic
44
Likely Pathogenic
99
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
234
0
234
Likely Pathogenic
0
0
44
0
44
VUS
0
89
10
0
99
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total0932880381

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

View in ClinVar →

Protein Context — Lollipop Plot

HIRIP3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Expression of Genes in the 16p11.2 Locus during Development of the Human Fetal Cerebral Cortex
Morson S et al.·Cereb Cortex
2021
Mechanism of action and experimental validation of key genes common to diabetic retinopathy and coronary heart disease based on multiple bioinformatics investigations
Jiang F et al.·Front Genet
2025Functional
A Rare Triplication of 16p11.2: Unravelling the Genomic Complexity and review of the literature.
van der Laan L et al.·Eur J Med Genet
2025Review
Dissecting the autism-associated 16p11.2 locus identifies multiple drivers in neuroanatomical phenotypes and unveils a male-specific role for the major vault protein
Kretz PF et al.·Genome Biol
2023
Three case reports of patients indicating the diversity of molecular and clinical features of 16p11.2 microdeletion anomaly
Szelest M et al.·BMC Med Genomics
2021Cohort
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients