HIRIP3

Chr 16

HIRA interacting protein 3

NCBI Gene: 8479 ENSG00000149929 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

The HIRA protein shares sequence similarity with Hir1p and Hir2p, the two corepressors of histone gene transcription characterized in the yeast, Saccharomyces cerevisiae. The structural features of the HIRA protein suggest that it may function as part of a multiprotein complex. Several cDNAs encoding HIRA-interacting proteins, or HIRIPs, have been identified. In vitro, the protein encoded by this gene binds HIRA, as well as H2B and H3 core histones, indicating that a complex containing HIRA-HIRIP3 could function in some aspects of chromatin and histone metabolism. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

LOEUF 0.87

Clinical Summary— HIRIP3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

89 VUS of 107 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 OE?0.55 (0.35–0.87)

0≤0.351.4

Missense OE?1.13 (1.03–1.23)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 13 / 23.8Missense obs/exp: 366 / 324.4Syn Z: -0.93

ClinVar Variant Classifications

107 submitted variants in ClinVar

ClinVar

Classification Summary

VUS89

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	89	89
Likely Benign	4	4
Benign	0	0
Total	93	93

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

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281 pathogenic / likely-pathogenic (of 299) ClinVar copy-number / structural variants overlap HIRIP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →