HNRNPDL

Summary

HNRNPDL (heterogeneous nuclear ribonucleoprotein D like, HGNC:5037) is a protein-coding gene on chromosome 4q21.22, encoding Heterogeneous nuclear ribonucleoprotein D-like (O14979). Acts as a transcriptional regulator.

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA 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 RRM domains that bind to RNAs. Three alternatively spliced transcript variants have been described for this gene. One of the variants is probably not translated because the transcript is a candidate for nonsense-mediated mRNA decay. The protein isoforms encoded by this gene are similar to its family member HNRPD.

Source: NCBI Gene 9987 — RefSeq curated summary.

At a glance

• Gene–disease (curated): muscular dystrophy, limb-girdle, autosomal dominant (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 505 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_031372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5037
Approved symbol	HNRNPDL
Name	heterogeneous nuclear ribonucleoprotein D like
Location	4q21.22
Locus type	gene with protein product
Status	Approved
Aliases	JKTBP, laAUF1
Ensembl gene	ENSG00000152795
Ensembl biotype	protein_coding
OMIM	607137
Entrez	9987

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 4 nonsense_mediated_decay

ENST00000295470, ENST00000349655, ENST00000502762, ENST00000507721, ENST00000514511, ENST00000602300, ENST00000614627, ENST00000621267, ENST00000630114, ENST00000630827, ENST00000880337, ENST00000880338, ENST00000880339, ENST00000918642, ENST00000918643, ENST00000918644, ENST00000958842

RefSeq mRNA: 2 — MANE Select: NM_031372 NM_001207000, NM_031372

CCDS: CCDS3593, CCDS75153

Canonical transcript exons

ENST00000295470 — 8 exons

Exon	Start	End
ENSE00001073166	82426037	82426129
ENSE00001073168	82428018	82428179
ENSE00001073177	82428278	82428446
ENSE00001295120	82429248	82430462
ENSE00001358882	82422569	82424883
ENSE00003484160	82426463	82426633
ENSE00003669464	82427190	82427304
ENSE00003681649	82427433	82427564

Expression profiles

Bgee: expression breadth ubiquitous, 306 present calls, max score 99.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 239.0478 / max 2913.7837, expressed in 1825 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52846	191.9069	1823
52845	21.1209	1784
52853	10.1577	1675
52850	6.6241	1659
52851	5.6909	1640
52844	1.3057	444
52843	1.0354	658
52849	0.5386	248
52852	0.2437	110
52854	0.1790	64

Top tissues by expression

306 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.73	gold quality
tendon of biceps brachii	UBERON:0008188	99.69	gold quality
embryo	UBERON:0000922	99.54	gold quality
ganglionic eminence	UBERON:0004023	99.54	gold quality
ventricular zone	UBERON:0003053	99.45	gold quality
cortical plate	UBERON:0005343	99.45	gold quality
tendon	UBERON:0000043	99.43	gold quality
left ovary	UBERON:0002119	99.42	gold quality
right ovary	UBERON:0002118	99.38	gold quality
cartilage tissue	UBERON:0002418	99.36	gold quality
body of uterus	UBERON:0009853	99.36	gold quality
medial globus pallidus	UBERON:0002477	99.35	gold quality
endocervix	UBERON:0000458	99.30	gold quality
nerve	UBERON:0001021	99.30	gold quality
tibial nerve	UBERON:0001323	99.30	gold quality
calcaneal tendon	UBERON:0003701	99.30	gold quality
body of pancreas	UBERON:0001150	99.29	gold quality
left uterine tube	UBERON:0001303	99.28	gold quality
right lung	UBERON:0002167	99.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.27	gold quality
ovary	UBERON:0000992	99.25	gold quality
amniotic fluid	UBERON:0000173	99.24	gold quality
metanephros cortex	UBERON:0010533	99.24	gold quality
ectocervix	UBERON:0012249	99.24	gold quality
lower esophagus	UBERON:0013473	99.23	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.23	gold quality
left lobe of thyroid gland	UBERON:0001120	99.22	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.21	gold quality
granulocyte	CL:0000094	99.20	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	23.78
E-MTAB-10042	yes	10.16
E-GEOD-130148	yes	4.54
E-MTAB-10137	no	3314.02
E-GEOD-124858	no	796.64
E-HCAD-4	no	30.01
E-MTAB-8271	no	6.96
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 12)

• Study shows that there is interaction of the intracellular domain of beta-amyloid precursor protein with JKTBP2, indicating that JKTBP2 may have an important function in AD formation. (PMID:16011250)
• The data of this study show that JKTBP1 and the 14-nt element act independently to mediate NRF internal ribosome entry segment activity. (PMID:17592041)
• overexpression of JKTBP1 in LNCaP cells leads to abnormal cell proliferation (PMID:18381662)
• The results indicate that JKTBP1 regulates the level of NRF protein expression by binding to both NRF 5’ and 3’ UTRs. (PMID:21300069)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• hnRNP DL and CNBP are novel antigens for SLE patients (PMID:23642268)
• A defect in the RNA-processing protein HNRPDL causes limb-girdle muscular dystrophy 1G. (PMID:24647604)
• Both hnRNP D and DL are able to control their own expression by alternative splicing of cassette exons in their 3’UTRs. Exon inclusion produces mRNAs degraded by nonsense-mediated decay. Moreover, hnRNP D and DL control the expression of one another by the same mechanism. (PMID:29263134)
• Heterogeneous nuclear ribonucleoprotein D-like (HNRPDL) is aberrantly expressed in specimens from colorectal cancer patients. (PMID:30052712)
• High HNRNPDL expression is associated with cervical cancer. (PMID:30447347)
• HNRPDL transforms hematopoietic cells and a novel HNRPDL/PBX1 axis plays an important role in human CML CD34(+) cells (PMID:31488872)
• Cryo-EM structure of hnRNPDL-2 fibrils, a functional amyloid associated with limb-girdle muscular dystrophy D3. (PMID:36646699)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	hnrnpdl	ENSDARG00000003429

Paralogs (36): DAZAP1 (ENSG00000071626), CIRBP (ENSG00000099622), RBM23 (ENSG00000100461), RBM3 (ENSG00000102317), NCL (ENSG00000115053), TIA1 (ENSG00000116001), HNRNPA2B1 (ENSG00000122566), RBM19 (ENSG00000122965), RBM39 (ENSG00000131051), MSI1 (ENSG00000135097), HNRNPA1 (ENSG00000135486), HNRNPD (ENSG00000138668), HNRNPA1L2 (ENSG00000139675), RBMX (ENSG00000147274), A1CF (ENSG00000148584), TIAL1 (ENSG00000151923), RBM46 (ENSG00000151962), MSI2 (ENSG00000153944), RBM47 (ENSG00000163694), RBMY1F (ENSG00000169800), HNRNPA3 (ENSG00000170144), RBMXL2 (ENSG00000170748), RBM4B (ENSG00000173914), RBM4 (ENSG00000173933), RBMXL3 (ENSG00000175718), HNRNPA0 (ENSG00000177733), TRNAU1AP (ENSG00000180098), HNRNPAB (ENSG00000197451), RBMXL1 (ENSG00000213516), HNRNPA1L3 (ENSG00000224578), RBMY1J (ENSG00000226941), RBMY1A1 (ENSG00000234414), RBMY1E (ENSG00000242389), RBMY1B (ENSG00000242875), RBMY1D (ENSG00000244395), DND1 (ENSG00000256453)

Protein

Protein identifiers

Heterogeneous nuclear ribonucleoprotein D-like — O14979 (reviewed: O14979)

Alternative names: AU-rich element RNA-binding factor, JKT41-binding protein, Protein laAUF1

All UniProt accessions (3): O14979, A0A087WU03, A0A087WUK2

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional regulator. Promotes transcription repression. Promotes transcription activation in differentiated myotubes. Binds to double- and single-stranded DNA sequences. Binds to the transcription suppressor CATR sequence of the COX5B promoter. 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.

Subunit / interactions. Interacts with ZNF148. Interacts with TNPO1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocytes. Expressed in myeloid leukemia, gastric adenocarcinoma, cervical carcinoma, hepatoma, fibrosarcoma, colon adenocarcinoma, epidermoid carcinoma, osteosarcoma and urinary bladder carcinoma cells.

Post-translational modifications. Dimethylation of Arg-408 is probably of the asymmetric type.

Disease relevance. Muscular dystrophy, limb-girdle, autosomal dominant 3 (LGMDD3) [MIM:609115] An autosomal dominant degenerative myopathy characterized by slowly progressive wasting and weakness of the proximal muscles of arms and legs around the pelvic or shoulder girdles, elevated creatine kinase levels and dystrophic features on muscle biopsy. LGMDD3 is characterized by a mild late-onset and is associated with progressive fingers and toes flexion limitation. Affected individuals may also develop cataracts before age 50. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in macrophages and retinoic acid (RA) in granulocytes (at protein level). Down-regulated by IL4/interleukin-4.

Isoforms (3)

UniProt ID	Names	Canonical?
O14979-1	1, JKTBP2	yes
O14979-2	2, JKTBP1
O14979-3	3

RefSeq proteins (2): NP_001193929, NP_112740* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034847	hnRPDL_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (28 total): modified residue 6, region of interest 6, strand 5, domain 2, compositionally biased region 2, splice variant 2, sequence variant 2, chain 1, cross-link 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7ZIR	ELECTRON MICROSCOPY	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14979-F1	63.01	0.15

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 25, 161, 216, 241, 408, 408, 209

Mutagenesis-validated functional residues (1):

Position	Phenotype
404	reduces significantly its nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation

MSigDB gene sets: 275 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, RNGTGGGC_UNKNOWN, AAGCAAT_MIR137, JI_RESPONSE_TO_FSH_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_255, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_317, CAGCTG_AP4_Q5, WEI_MYCN_TARGETS_WITH_E_BOX, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP

GO Biological Process (2): RNA processing (GO:0006396), regulation of gene expression (GO:0010468)

GO Molecular Function (8): DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), poly(A) binding (GO:0008143), poly(G) binding (GO:0034046), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytosol (GO:0005829), cytoplasm (GO:0005737), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interleukin-12 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
gene expression	2
nucleic acid binding	2
DNA binding	2
poly-purine tract binding	2
binding	2
RNA biosynthetic process	1
primary metabolic process	1
regulation of macromolecule biosynthetic process	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
cytoplasm	1
intracellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

4070 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HNRNPDL	PTBP1	P26599	929
HNRNPDL	HNRNPM	P52272	905
HNRNPDL	HNRNPU	Q00839	863
HNRNPDL	HNRNPL	P14866	842
HNRNPDL	HNRNPF	P52597	821
HNRNPDL	HNRNPK	P61978	820
HNRNPDL	RAVER1	Q8IY67	816
HNRNPDL	HNRNPH1	P31943	804
HNRNPDL	FUS	P35637	801
HNRNPDL	MYC	P01106	796
HNRNPDL	TARDBP	Q13148	787
HNRNPDL	SRSF2	Q01130	780
HNRNPDL	PKM	P14618	775
HNRNPDL	PCBP1	Q15365	769
HNRNPDL	DGCR8	Q8WYQ5	761

IntAct

249 interactions, top by confidence:

A	B	Type	Score
HNRNPC	KPNA3	psi-mi:“MI:0914”(association)	0.850
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
HNRNPDL	SNRPC	psi-mi:“MI:0915”(physical association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
HNRNPA2B1	HNRNPDL	psi-mi:“MI:0915”(physical association)	0.560
HNRNPDL	HNRNPD	psi-mi:“MI:0915”(physical association)	0.560
HNRNPDL	WFS1	psi-mi:“MI:0915”(physical association)	0.560
HNRNPDL	TARDBP	psi-mi:“MI:0915”(physical association)	0.560
HNRNPD	HNRNPDL	psi-mi:“MI:0914”(association)	0.560
NONO	HNRNPDL	psi-mi:“MI:0915”(physical association)	0.540
N	HNRNPDL	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
UTP20	HNRNPDL	psi-mi:“MI:0915”(physical association)	0.400
ADCK1	HNRNPDL	psi-mi:“MI:0915”(physical association)	0.400
PRDM13	HNRNPDL	psi-mi:“MI:0915”(physical association)	0.400
RNF32	HNRNPDL	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (550): HNRNPDL (Affinity Capture-MS), HNRNPDL (Affinity Capture-MS), HNRNPDL (Affinity Capture-MS), HNRNPDL (Affinity Capture-MS), HNRNPDL (Affinity Capture-MS), HNRNPDL (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), YARS2 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), MRPL32 (Affinity Capture-MS), ERAL1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), MRPS9 (Affinity Capture-MS), NGRN (Affinity Capture-MS), SUPV3L1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IZ84, A1L020, B3P8A3, B4K799, E1BB52, F1LP90, F4JCU0, G5EFS2, O14979, O43347, O75175, O80567, O94432, Q09285, Q14103, Q17RY0, Q28CH2, Q2HJG4, Q3SWU3, Q4PA86, Q5ZI72, Q60668, Q61474, Q6E3D2, Q6E3D4, Q6NU14, Q6NYG6, Q6ZK57, Q7SXN4, Q7TN98, Q7TN99, Q7Z5Q1, Q812E0, Q86U06, Q8CGZ0, Q8I0P1, Q8K0V4, Q8K3P4, Q8NE35, Q91W18

Diamond homologs: A0A0D1C8Z4, A0A2R8Y4L2, A5A6H4, A7VJC2, D0VWM8, G5EFS2, O14979, O43347, O88569, O89086, O93235, O94432, P04256, P07909, P09405, P09651, P09867, P13383, P17130, P19338, P19682, P19683, P21522, P22626, P28644, P41891, P48809, P48810, P49312, P51968, P51989, P51990, P51991, P51992, P60824, P60825, P60826, P98179, Q02926, Q03878

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA Polyadenylation	19	13.3×	5e-14
Processing of Capped Intron-Containing Pre-mRNA	18	11.8×	2e-12
mRNA Splicing - Major Pathway	23	10.1×	3e-14
mRNA Splicing	10	8.8×	3e-05
Dengue Virus-Host Interactions	18	6.6×	4e-08
Neddylation	12	4.5×	1e-03
Metabolism of RNA	13	4.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	5	33.0×	7e-05
alternative mRNA splicing, via spliceosome	5	22.5×	3e-04
intrinsic apoptotic signaling pathway	7	16.7×	5e-05
regulation of alternative mRNA splicing, via spliceosome	10	16.3×	3e-07
autophagosome maturation	6	14.0×	4e-04
mRNA splicing, via spliceosome	22	13.4×	1e-15
mRNA transport	7	12.3×	2e-04
G1/S transition of mitotic cell cycle	8	10.7×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

505 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	277
Likely benign	180
Benign	19

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
830313	Single allele	Pathogenic
1701471	NM_031372.4(HNRNPDL):c.115_116delinsTT (p.Ala39Phe)	Likely pathogenic
814577	GRCh37/hg19 4q21.22(chr4:83026373-83367140)x1	Likely pathogenic

SpliceAI

1048 predictions. Top by Δscore:

Variant	Effect	Δscore
4:82424881:CTC:C	acceptor_gain	1.0000
4:82424884:C:A	acceptor_loss	1.0000
4:82424884:C:CC	acceptor_gain	1.0000
4:82424885:T:C	acceptor_loss	1.0000
4:82425474:A:AC	donor_gain	1.0000
4:82425474:AAT:A	donor_gain	1.0000
4:82425474:AATCT:A	donor_gain	1.0000
4:82425475:A:C	donor_gain	1.0000
4:82425532:CG:C	donor_gain	1.0000
4:82426129:CC:C	acceptor_loss	1.0000
4:82426130:C:CC	acceptor_gain	1.0000
4:82426130:CT:C	acceptor_loss	1.0000
4:82426131:T:G	acceptor_loss	1.0000
4:82426135:T:C	acceptor_gain	1.0000
4:82426135:T:TC	acceptor_gain	1.0000
4:82426457:TCTTA:T	donor_loss	1.0000
4:82426458:CTTA:C	donor_loss	1.0000
4:82426459:TTA:T	donor_loss	1.0000
4:82426460:TACCA:T	donor_loss	1.0000
4:82426461:A:AC	donor_gain	1.0000
4:82426461:A:C	donor_loss	1.0000
4:82426462:C:CC	donor_gain	1.0000
4:82426462:C:T	donor_loss	1.0000
4:82426462:CCA:C	donor_gain	1.0000
4:82426629:CTGAC:C	acceptor_gain	1.0000
4:82426630:TGAC:T	acceptor_gain	1.0000
4:82426631:GAC:G	acceptor_gain	1.0000
4:82426632:AC:A	acceptor_gain	1.0000
4:82426633:CC:C	acceptor_gain	1.0000
4:82426635:T:G	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS10002169 (4:82429944 G>A,C), RS1000840435 (4:82428953 G>A), RS1001001656 (4:82424017 A>C), RS1001115683 (4:82431165 C>A,G,T), RS1001292739 (4:82429144 G>A,C), RS1001839263 (4:82429367 C>A,G,T), RS1002064105 (4:82430084 G>A,T), RS1002116296 (4:82430258 C>T), RS1002229610 (4:82425220 G>C), RS10024950 (4:82429576 C>A,T), RS10026631 (4:82425953 T>C), RS1002685086 (4:82425890 T>A,C), RS1002731820 (4:82428704 A>C,T), RS1002892347 (4:82426945 T>C), RS1003224151 (4:82425503 A>G)

Disease associations

OMIM: gene MIM:607137 | disease phenotypes: MIM:609115, MIM:613509

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant limb-girdle muscular dystrophy type 1G	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
muscular dystrophy, limb-girdle, autosomal dominant	Definitive	AD

Mondo (2): autosomal dominant limb-girdle muscular dystrophy type 1G (MONDO:0012193), chromosome 4q21 deletion syndrome (MONDO:0013292)

Orphanet (2): HNRNPDL-related limb-girdle muscular dystrophy D3 (Orphanet:55596), 4q21 microdeletion syndrome (Orphanet:238750)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000518	Cataract
HP:0001265	Hyporeflexia
HP:0003198	Myopathy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003547	Shoulder girdle muscle weakness
HP:0003581	Adult onset
HP:0003677	Slowly progressive
HP:0003749	Pelvic girdle muscle weakness
HP:0003805	Rimmed vacuoles
HP:0003829	Typified by incomplete penetrance
HP:0006203	Decreased movement range in interphalangeal joints
HP:0006785	Limb-girdle muscular dystrophy
HP:0008116	Flexion limitation of toes
HP:0008948	Proximal upper limb amyotrophy
HP:0008956	Proximal lower limb amyotrophy

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563794	Limb-Girdle Muscular Dystrophy, Type 1G (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067050 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.16	Kd	68.54	nM	CHEMBL3752910
7.16	ED50	68.54	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149872: Binding affinity to human HNRNPDL incubated for 45 mins by Kinobead based pull down assay	kd	0.0685	uM

CTD chemical–gene interactions

72 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	4
bisphenol A	decreases expression	3
sodium arsenite	affects cotreatment, increases expression, decreases expression	2
Caffeine	increases phosphorylation, decreases expression	2
Formaldehyde	decreases expression	2
Tretinoin	affects cotreatment, increases expression	2
Valproic Acid	affects expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
tert-Butylhydroperoxide	affects cotreatment, increases expression, decreases reaction, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
lead acetate	decreases expression	1
decabromobiphenyl ether	increases expression	1
arsenite	increases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	affects expression, decreases expression	1
tetrabromobisphenol A	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
diallyl trisulfide	increases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652914	Binding	Binding affinity to human HNRNPDL incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1TS	Abcam HeLa HNRNPDL KO	Cancer cell line	Female
CVCL_SR59	HAP1 HNRNPDL (-) 1	Cancer cell line	Male
CVCL_SR60	HAP1 HNRNPDL (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments