HNRNPH1

Chr 5AD

heterogeneous nuclear ribonucleoprotein H1

Also known as: HNRPH, HNRPH1, NEDCDS, hnRNPH

HNRNPH1 encodes a heterogeneous nuclear ribonucleoprotein that binds RNA and regulates pre-mRNA alternative splicing, serving as a component of hnRNP complexes that process pre-mRNAs before they become functional cytoplasmic mRNAs. Mutations cause autosomal dominant neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.11), indicating intolerance to reduced gene dosage.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.111 OMIM phenotype
Clinical SummaryHNRNPH1
🧬
Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 4.84
OE 0.00 (0.000.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
4.09Z-score
OE missense 0.29 (0.240.35)
74 obs / 259.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.11)
00.351.4
Missense OE0.29 (0.240.35)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 0 / 27.3Missense obs/exp: 74 / 259.3Syn Z: -0.08
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongHNRNPH1-related neurodevelopmental disorderLOFAD
DN
0.3892th %ile
GOF
0.4580th %ile
LOF
0.76top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.11

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HNRNPH1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗