HNRNPDL

Chr 4AD

heterogeneous nuclear ribonucleoprotein D like

Also known as: HNRNP, HNRPDL, JKTBP, JKTBP2, LGMD1G, LGMDD3, laAUF1

NCBI Gene: 9987ENSG00000152795UniProt: O14979OMIM: 607137

The protein binds RNA through two RRM domains and regulates pre-mRNA processing and mRNA metabolism in the nucleus. Mutations cause limb-girdle muscular dystrophy type 3 with autosomal dominant inheritance. The pathogenic mechanism involves disrupted RNA processing that leads to progressive muscle weakness and atrophy primarily affecting the shoulder and pelvic girdle muscles.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismADLOEUF 0.551 OMIM phenotype
Clinical Summary— HNRNPDL
🧬
Gene-Disease Validity (ClinGen)
muscular dystrophy, limb-girdle, autosomal dominant · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 128 VUS of 245 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
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
0.70Z-score
OE missense 0.86 (0.77–0.98)
182 obs / 210.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.15–0.55)
0≤0.351.4
Missense OE0.86 (0.77–0.98)
0≤0.61.4
Synonymous OE1.62
0≤1.21.6
LoF obs/exp: 6 / 21.4Missense obs/exp: 182 / 210.6Syn Z: -4.33
DN
0.7033th %ile
GOF
0.5269th %ile
LOF
0.4529th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

245 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic5
VUS128
Likely Benign76
Benign6
Conflicting4
16
Pathogenic
5
Likely Pathogenic
128
VUS
76
Likely Benign
6
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
2
3
0
5
VUS
7
111
9
1
128
Likely Benign
0
0
22
54
76
Benign
0
1
1
4
6
Conflicting
—4
Total71145159235

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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