HNRNPDL

Chr 4AD

heterogeneous nuclear ribonucleoprotein D like

NCBI Gene: 9987ENSG00000152795UniProt: O14979

Acts as a transcriptional regulator. Promotes transcription repression. Promotes transcription activation in differentiated myotubes (By similarity). Binds to double- and single-stranded DNA sequences. Binds to the transcription suppressor CATR sequence of the COX5B promoter (By similarity). Binds with high affinity to RNA molecules that contain AU-rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Binds both to nuclear and cytoplasmic poly(A) mRNAs. Binds to poly(G) and poly(A), but not to poly(U) or poly(C) RNA homopolymers. Binds to the 5'-ACUAGC-3' RNA consensus sequence

Primary Disease Associations & Inheritance

Muscular dystrophy, limb-girdle, autosomal dominant 3MIM #609115
AD
543
ClinVar variants
31
Pathogenic / LP
0.08
pLI score
0
Active trials
Clinical Summary— HNRNPDL
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 233 VUS of 543 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.55LOEUF
pLI 0.078
Z-score 3.09
OE 0.28 (0.15–0.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.70Z-score
OE missense 0.86 (0.77–0.98)
182 obs / 210.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.28 (0.15–0.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.77–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.62
0≤1.21.6
LoF obs/exp: 6 / 21.4Missense obs/exp: 182 / 210.6Syn Z: -4.33

ClinVar Variant Classifications

543 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic6
VUS233
Likely Benign149
Benign16
Conflicting4
25
Pathogenic
6
Likely Pathogenic
233
VUS
149
Likely Benign
16
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
3
3
0
6
VUS
8
200
22
3
233
Likely Benign
0
0
40
109
149
Benign
0
1
12
3
16
Conflicting
—4
Total8204102115433

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

View in ClinVar →

Protein Context — Lollipop Plot

HNRNPDL · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Muscular dystrophy, limb-girdle, autosomal dominant 3

MIM #609115

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TRIM4 modulates the ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitor in ovarian cancer.
Che X et al.·Front Med
2025
HNRNPDL-related muscular dystrophy: expanding the clinical, morphological and MRI phenotypes.
Berardo A et al.·J Neurol
2019Case report
Hsa_circ_0038737 promotes PARPi resistance in castration-resistant prostate cancer via IGF2BP3-mediated DNPH1 mRNA stabilization.
Wang Z et al.·Mol Cancer
2025
Genome-wide analysis of abnormal splicing regulators and alternative splicing involved in immune regulation in systemic lupus erythematosus.
Xu B et al.·Autoimmunity
2025
Myopathies with finger flexor weakness: Not only inclusion-body myositis.
Nicolau S et al.·Muscle Nerve
2020Review
Mutations in human prion-like domains: pathogenic but not always amyloidogenic.
Bartolomé-Nafría A et al.·Prion
2024Review
Clinical features, mutation spectrum and factors related to reaching molecular diagnosis in a cohort of patients with distal myopathies.
Muelas N et al.·J Neurol
2025Cohort
Proteomic studies in VWA1-related neuromyopathy allowed new pathophysiological insights and the definition of blood biomarkers.
Athamneh M et al.·J Cell Mol Med
2024
Further defining the critical genes for the 4q21 microdeletion disorder.
Hu X et al.·Am J Med Genet A
2017Case report
Limb girdle muscular dystrophy D3 HNRNPDL related in a Chinese family with distal muscle weakness caused by a mutation in the prion-like domain.
Sun Y et al.·J Neurol
2019Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools