HNRNPH2

Chr XXLD

heterogeneous nuclear ribonucleoprotein H2

Also known as: FTP3, HNRPH', HNRPH2, MRXSB, NRPH2, hnRNPH'

NCBI Gene: 3188ENSG00000126945UniProt: P55795OMIM: 300610

The protein binds to RNA through three quasi-RRM domains and influences pre-mRNA processing and other aspects of mRNA metabolism and transport in the nucleus. Loss-of-function mutations cause X-linked syndromic intellectual developmental disorder, Bain type, following an X-linked dominant inheritance pattern. The high pLI score (0.95) and low LOEUF score (0.31) indicate strong intolerance to loss-of-function variants, consistent with the pathogenic mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismXLDLOEUF 0.311 OMIM phenotype
Clinical Summary— HNRNPH2
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Gene-Disease Validity (ClinGen)
X-linked complex neurodevelopmental disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.31LOEUF
pLI 0.954
Z-score 2.89
OE 0.00 (0.00–0.31)
Highly constrained

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

Missense Constraint
3.62Z-score
OE missense 0.24 (0.18–0.30)
42 obs / 178.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.31)
0≤0.351.4
Missense OE0.24 (0.18–0.30)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 0 / 9.7Missense obs/exp: 42 / 178.1Syn Z: 0.33
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongHNRNPH2-related neurodevelopmental disorderOTHERmonoallelic_X_heterozygous
DN
0.3495th %ile
GOF
0.4382th %ile
LOF
0.78top 5%

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

LOFprediction above median · LOEUF 0.31

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

ClinVar

Protein Context — Lollipop Plot

HNRNPH2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Preclinical evaluation of antisense oligonucleotide therapy in a mouse model of HNRNPH2-related neurodevelopmental disorder.
Korff A et al.·Sci Transl Med
2026Functional
HNRNPH2 variant linked to intellectual disability disrupts myelination by impairing oligodendrocyte differentiation.
Jiao Y et al.·J Genet Genomics
2025
Reactivation of Human X-Linked Gene and Stable X-Chromosome Inactivation Observed in Generation and Differentiation of iPSCs from a Female Patient with HNRNPH2 Mutation.
Chen G et al.·Cells
2025Open Access
Novel enhancer mediates the RPL36A-HNRNPH2 readthrough loci and GLA gene expressions associated with fabry disease.
Al-Obaide MA et al.·Front Genet
2023Open Access
A Prospective, Longitudinal Study of Caregiver-Reported Adaptive Skills and Function of Individuals with HNRNPH2-related Neurodevelopmental Disorder.
Davis TJ et al.·Adv Neurodev Disord
2024Open AccessNatural history
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