HNRNPD

Chr 4

heterogeneous nuclear ribonucleoprotein D

Also known as: AUF1, AUF1A, HNRPD, P37, hnRNPD0

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are nucleic acid binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two repeats of quasi-RRM domains that bind to RNAs. It localizes to both the nucleus and the cytoplasm. This protein is implicated in the regulation of mRNA stability. Alternative splicing of this gene results in four transcript variants. [provided by RefSeq, Jul 2008]

2
Active trials
11
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.23
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical SummaryHNRNPD
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · 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.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.996
Z-score 4.03
OE 0.05 (0.020.23)
Highly constrained

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

Missense Constraint
2.45Z-score
OE missense 0.49 (0.410.59)
91 obs / 184.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.020.23)
00.351.4
Missense OE0.49 (0.410.59)
00.61.4
Synonymous OE0.77
01.21.6
LoF obs/exp: 1 / 20.9Missense obs/exp: 91 / 184.8Syn Z: 1.47
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateHNRNPD-related developmental disorderLOFAD
DN
0.3594th %ile
GOF
0.2796th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.23

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

HNRNPD · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC