HNRNPR

Summary

HNRNPR (heterogeneous nuclear ribonucleoprotein R, HGNC:5047) is a protein-coding gene on chromosome 1p36.12, encoding Heterogeneous nuclear ribonucleoprotein R (O43390). Component of ribonucleosomes, which are complexes of at least 20 other different heterogeneous nuclear ribonucleoproteins (hnRNP). hnRNP play an important role in processing of precursor mRNA in the nucleus. It is a selective cancer dependency (DepMap: 18.5% of cell lines).

This gene encodes an RNA-binding protein that is a member of the spliceosome C complex, which functions in pre-mRNA processing and transport. The encoded protein also promotes transcription at the c-fos gene. Alternative splicing results in multiple transcript variants. There are pseudogenes for this gene on chromosomes 4, 11, and 10.

Source: NCBI Gene 10236 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 105 total — 5 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 49
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 18.5% of screened cell lines
• MANE Select transcript: NM_005826

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5047
Approved symbol	HNRNPR
Name	heterogeneous nuclear ribonucleoprotein R
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	hnRNP-R
Ensembl gene	ENSG00000125944
Ensembl biotype	protein_coding
OMIM	607201
Entrez	10236

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 25 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000302271, ENST00000374612, ENST00000374616, ENST00000463552, ENST00000464516, ENST00000470941, ENST00000476451, ENST00000476660, ENST00000478691, ENST00000490652, ENST00000606561, ENST00000641107, ENST00000675048, ENST00000882591, ENST00000882592, ENST00000882593, ENST00000882594, ENST00000882595, ENST00000882596, ENST00000882597, ENST00000934773, ENST00000934774, ENST00000934775, ENST00000934776, ENST00000934777, ENST00000934778, ENST00000934779, ENST00000947104, ENST00000947105

RefSeq mRNA: 7 — MANE Select: NM_005826 NM_001102397, NM_001102398, NM_001102399, NM_001297620, NM_001297621, NM_001297622, NM_005826

CCDS: CCDS232, CCDS44085, CCDS60020, CCDS72726, CCDS72727

Canonical transcript exons

ENST00000302271 — 11 exons

Exon	Start	End
ENSE00001888851	23304688	23311066
ENSE00001957950	23344211	23344284
ENSE00003471374	23313553	23313702
ENSE00003520254	23321528	23321663
ENSE00003546725	23333518	23333631
ENSE00003557507	23311201	23311322
ENSE00003603207	23338490	23338608
ENSE00003605888	23318483	23318688
ENSE00003618755	23323556	23323732
ENSE00003689484	23337754	23337861
ENSE00003690057	23340852	23341017

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.6908 / max 2127.3404, expressed in 1818 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10955	56.0863	1816
10954	6.6132	1592
10958	2.2412	1282
10957	2.0121	1163
10956	0.4912	293
10959	0.2467	104

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.20	gold quality
embryo	UBERON:0000922	99.18	gold quality
ganglionic eminence	UBERON:0004023	99.18	gold quality
cortical plate	UBERON:0005343	98.89	gold quality
calcaneal tendon	UBERON:0003701	97.98	gold quality
vermiform appendix	UBERON:0001154	97.65	gold quality
smooth muscle tissue	UBERON:0001135	97.55	gold quality
colonic epithelium	UBERON:0000397	97.48	gold quality
islet of Langerhans	UBERON:0000006	97.14	gold quality
rectum	UBERON:0001052	97.14	gold quality
monocyte	CL:0000576	96.97	gold quality
leukocyte	CL:0000738	96.94	gold quality
adrenal tissue	UBERON:0018303	96.92	gold quality
left ovary	UBERON:0002119	96.78	gold quality
left uterine tube	UBERON:0001303	96.68	gold quality
right ovary	UBERON:0002118	96.63	gold quality
stromal cell of endometrium	CL:0002255	96.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.59	gold quality
body of uterus	UBERON:0009853	96.56	gold quality
ectocervix	UBERON:0012249	96.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.47	gold quality
bone marrow cell	CL:0002092	96.29	gold quality
endocervix	UBERON:0000458	96.14	gold quality
granulocyte	CL:0000094	96.11	gold quality
skin of abdomen	UBERON:0001416	95.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.94	gold quality
gall bladder	UBERON:0002110	95.81	gold quality
tibial nerve	UBERON:0001323	95.76	gold quality
left adrenal gland cortex	UBERON:0035825	95.72	gold quality
left adrenal gland	UBERON:0001234	95.66	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ASCL1	Unknown

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

258 targeting HNRNPR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-12136	99.98	72.81	5713

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• validated occurrence of an unusual TG 3’ splice site in intron 7 (PMID:17672918)
• HNRNPR enhanced transcription from the c-fos promoter. (PMID:19581295)
• Data demonstrate that expression levels of hnRNP A1, Q, K, R, and U influence HIV-1 production by persistently infected astrocytes, linking these hnRNPs to HIV replication. (PMID:19808671)
• Short-term exercise resulted in a significant increase of mRNA expression of genes encoding proteins involved in the formation of precatalytic splisosome: HNRNPR. (PMID:19902070)
• SMN is involved in the axonal translocation of hnRNP R and hnRNP R-bound RNA/protein complexes. (PMID:25338097)
• demonstrated that HNRNPR binds MHC class I mRNAs in their 3’ untranslated regions and enhances their stability and their expression; regulation by HNRNPR modulates the cytotoxic activity of NK cell; conclude that HNRNPR acts as a general positive regulator of MHC class I expression (PMID:27194785)
• Identification of the frequent presence of hnRNP R and hnRNP Q in frontotemporal lobar degeneration (FTLD)-FUS inclusions suggests a potential role for these hnRNPs in FTLD-FUS pathogenesis and supports the role of dysfunctional RNA metabolism in FTLD. (PMID:30755280)
• HNRNPR Variants that Impair Homeobox Gene Expression causes Developmental Disorders. (PMID:31079900)
• HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis. (PMID:31527303)
• hnRNP R negatively regulates transcription by modulating the association of P-TEFb with 7SK and BRD4. (PMID:35856391)
• Pan-cancer analysis of the oncogenic role of HNRNPR in human tumors. (PMID:37077028)
• HNRNPA2B1 and HNRNPR stabilize ASCL1 in an m6A-dependent manner to promote neuroblastoma progression. (PMID:38331110)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hnrnpr	ENSDARG00000014569
mus_musculus	Hnrnpr	ENSMUSG00000066037
rattus_norvegicus	Hnrnpr	ENSRNOG00000011910
rattus_norvegicus	Hnrnpr-ps2	ENSRNOG00000048337

Paralogs (24): ELAVL1 (ENSG00000066044), PABPC1 (ENSG00000070756), RBMS2 (ENSG00000076067), PABPC4 (ENSG00000090621), PABPC1L (ENSG00000101104), ELAVL2 (ENSG00000107105), RBM24 (ENSG00000112183), TARDBP (ENSG00000120948), RBM38 (ENSG00000132819), SYNCRIP (ENSG00000135316), SF3B4 (ENSG00000143368), RBMS3 (ENSG00000144642), PABPC3 (ENSG00000151846), RBMS1 (ENSG00000153250), RBM45 (ENSG00000155636), ELAVL4 (ENSG00000162374), PABPC5 (ENSG00000174740), PUF60 (ENSG00000179950), PABPC1L2B (ENSG00000184388), PABPC1L2A (ENSG00000186288), RBM34 (ENSG00000188739), ELAVL3 (ENSG00000196361), RBM14 (ENSG00000239306), PABPC4L (ENSG00000254535)

Protein

Protein identifiers

Heterogeneous nuclear ribonucleoprotein R — O43390 (reviewed: O43390)

All UniProt accessions (7): O43390, A0A286YEZ8, A0A6Q8PEX7, A0A6Q8PH31, A0A6Q8PH35, A0A6Q8PHG0, B4DT28

UniProt curated annotations — full annotation on UniProt →

Function. Component of ribonucleosomes, which are complexes of at least 20 other different heterogeneous nuclear ribonucleoproteins (hnRNP). hnRNP play an important role in processing of precursor mRNA in the nucleus.

Subunit / interactions. Identified in the spliceosome C complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with GTPBP1.

Subcellular location. Nucleus. Microsome. Nucleoplasm. Cytoplasm.

Disease relevance. Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities (NEDDFSB) [MIM:620073] An autosomal dominant disorder characterized by global developmental delay with impaired intellectual development and poor or absent speech, corpus callosum structural defects and cerebellar hypoplasia on brain imaging, poor overall growth, facial dysmorphism, and skeletal defects. Variable additional findings include hypotonia, seizures, and ocular defects. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Expression is low and neural-specific.

Isoforms (4)

UniProt ID	Names	Canonical?
O43390-1	1	yes
O43390-2	2
O43390-3	3, hnRNP-R2
O43390-4	4

RefSeq proteins (7): NP_001095867, NP_001095868, NP_001095869, NP_001284549, NP_001284550, NP_001284551, NP_005817* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR006535	HnRNP_R/Q_splicing_fac	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034410	hnRNPR_RRM1	Domain
IPR034411	hnRNPR_RRM2	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR041337	hnRNP_Q_AcD	Domain

Pfam: PF00076, PF18360

UniProt features (39 total): compositionally biased region 8, region of interest 5, strand 4, domain 3, cross-link 3, splice variant 3, helix 3, repeat 3, modified residue 2, sequence variant 2, initiator methionine 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9EJY	X-RAY DIFFRACTION	1.9
2DK2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43390-F1	69.03	0.43

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 (5): 2, 366, 13, 171, 359

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 507 (showing top): E2F_Q4, CREL_01, MORF_DNMT1, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, MORF_SMC1L1, PAX4_01, E2F4DP1_01, LFA1_Q6, MAZ_Q6, MORF_RRM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MORF_HDAC1, MORF_UBE2N, MITSIADES_RESPONSE_TO_APLIDIN_DN, MORF_HDAC2

GO Biological Process (3): mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), catalytic step 2 spliceosome (GO:0071013), ribonucleoprotein complex (GO:1990904), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
mRNA Splicing	1
Metabolism of RNA	1
mRNA 3’-end processing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
binding	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1
protein-containing complex	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

2322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HNRNPR	GEMIN2	O14893	816
HNRNPR	KHSRP	Q92945	803
HNRNPR	HNRNPM	P52272	785
HNRNPR	ACTB	P02570	754
HNRNPR	HNRNPU	Q00839	744
HNRNPR	SMN1	Q16637	743
HNRNPR	HNRNPC	P07910	717
HNRNPR	HNRNPL	P14866	702
HNRNPR	HNRNPK	P61978	688
HNRNPR	FMR1	Q06787	668
HNRNPR	HNRNPA1	P09651	662
HNRNPR	HNRNPA3	P51991	660
HNRNPR	P3H3	Q8IVL6	652
HNRNPR	FBL	P22087	636
HNRNPR	IGF2BP1	Q9NZI8	608

IntAct

286 interactions, top by confidence:

A	B	Type	Score
HNRNPC	KPNA3	psi-mi:“MI:0914”(association)	0.850
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
HNRNPR	PRMT1	psi-mi:“MI:0915”(physical association)	0.740
PRMT1	HNRNPR	psi-mi:“MI:0915”(physical association)	0.740
N	HNRNPR	psi-mi:“MI:0914”(association)	0.730
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
HNRNPR	KHDRBS2	psi-mi:“MI:0915”(physical association)	0.560
KHDRBS2	HNRNPR	psi-mi:“MI:0915”(physical association)	0.560
HNRNPD	HNRNPDL	psi-mi:“MI:0914”(association)	0.560
N	RBM47	psi-mi:“MI:0914”(association)	0.530
YBX1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
ESR1		psi-mi:“MI:0914”(association)	0.460
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430
ABL1	HNRNPR	psi-mi:“MI:0915”(physical association)	0.400
HNRNPR	CRK	psi-mi:“MI:0915”(physical association)	0.400
FYN	HNRNPR	psi-mi:“MI:0915”(physical association)	0.400
GRB2	HNRNPR	psi-mi:“MI:0915”(physical association)	0.400
HNRNPR	NCK1	psi-mi:“MI:0915”(physical association)	0.400
ZNF644	HNRNPR	psi-mi:“MI:0915”(physical association)	0.400
PSTPIP1	HNRNPR	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (733): HNRNPR (Two-hybrid), KHDRBS2 (Two-hybrid), HNRNPR (Protein-peptide), HNRNPR (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), HNRNPR (Affinity Capture-MS)

ESM2 similar proteins: A1CRM1, A1D4K4, A2Q848, A3LXL0, A4QUF0, A5DM21, A5DW14, F1QB54, O22173, O43390, O60506, O64380, P04147, P0CP46, P0CP47, P11940, P20965, P21187, P29341, P31209, P42731, P61286, Q05196, Q0CR95, Q0U1G2, Q13310, Q1DXH0, Q2GSX8, Q2UK72, Q4P8R9, Q4WK03, Q54BM2, Q5AI15, Q5B630, Q5R8F7, Q6BI95, Q6CDH3, Q6CSV3, Q6DEY7, Q6FKG4

Diamond homologs: A0A8M1NHK4, A0AV96, A0JM51, A4FV72, A4QUF0, A8WLV5, O01671, O04425, O43040, O43390, O60506, P28659, P33240, P86049, Q08BH5, Q08E07, Q0P4R6, Q0V9L3, Q10B98, Q14498, Q28HE9, Q2HJG2, Q2UK72, Q3UEB3, Q4QQT3, Q4R2Z0, Q4R535, Q5B630, Q5EA36, Q5R469, Q5R5P4, Q5R723, Q5R9H4, Q5RC41, Q5RC80, Q5RDA3, Q5SZQ8, Q5YD48, Q66H68, Q6DCB7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 192 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
Metabolism of non-coding RNA	6	28.6×	4e-06
mRNA Polyadenylation	22	14.5×	6e-17
Processing of Capped Intron-Containing Pre-mRNA	20	12.3×	3e-14
SARS-CoV-2 modulates host translation machinery	7	11.8×	1e-04
mRNA Splicing - Minor Pathway	6	10.1×	1e-03
RNA Polymerase II Transcription Termination	6	9.9×	1e-03
mRNA Splicing - Major Pathway	24	9.9×	6e-15
snRNP Assembly	6	9.5×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	7	42.0×	5e-08
alternative mRNA splicing, via spliceosome	6	24.5×	1e-05
mRNA stabilization	8	17.8×	2e-06
spliceosomal snRNP assembly	5	17.6×	5e-04
regulation of alternative mRNA splicing, via spliceosome	11	16.3×	4e-08
negative regulation of translation	11	13.1×	1e-07
autophagosome maturation	6	12.8×	5e-04
mRNA splicing, via spliceosome	21	11.7×	1e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	3
Uncertain significance	73
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1710307	NM_005826.5(HNRNPR):c.1600dup (p.Ala534fs)	Pathogenic
1710308	NM_005826.5(HNRNPR):c.1643dup (p.Pro549fs)	Pathogenic
1710309	NM_005826.5(HNRNPR):c.1754G>A (p.Arg585His)	Pathogenic
2609054	NM_005826.5(HNRNPR):c.1599_1600dup (p.Ala534fs)	Pathogenic
3906508	NM_005826.5(HNRNPR):c.332_333del (p.Gln111fs)	Pathogenic
1346875	NM_005826.5(HNRNPR):c.1651C>T (p.Gln551Ter)	Likely pathogenic
4540100	NM_005826.5(HNRNPR):c.455C>A (p.Pro152Gln)	Likely pathogenic
520674	NM_005826.5(HNRNPR):c.1654C>T (p.Gln552Ter)	Likely pathogenic

SpliceAI

1645 predictions. Top by Δscore:

Variant	Effect	Δscore
1:23311066:CCTA:C	acceptor_loss	1.0000
1:23311068:T:A	acceptor_loss	1.0000
1:23311071:C:CT	acceptor_gain	1.0000
1:23311075:G:C	acceptor_gain	1.0000
1:23311075:G:GC	acceptor_gain	1.0000
1:23311194:GACTC:G	donor_loss	1.0000
1:23311195:AC:A	donor_loss	1.0000
1:23311196:C:CG	donor_loss	1.0000
1:23311197:T:TA	donor_loss	1.0000
1:23311198:CACGC:C	donor_loss	1.0000
1:23311199:A:AC	donor_gain	1.0000
1:23311199:ACG:A	donor_gain	1.0000
1:23311200:C:CA	donor_gain	1.0000
1:23311200:CG:C	donor_gain	1.0000
1:23311200:CGC:C	donor_gain	1.0000
1:23311200:CGCA:C	donor_gain	1.0000
1:23311319:TAGC:T	acceptor_gain	1.0000
1:23311320:AGC:A	acceptor_gain	1.0000
1:23311320:AGCCT:A	acceptor_loss	1.0000
1:23311321:GCCT:G	acceptor_loss	1.0000
1:23311323:C:CC	acceptor_gain	1.0000
1:23311323:CT:C	acceptor_loss	1.0000
1:23313550:TACC:T	donor_loss	1.0000
1:23313551:A:AC	donor_gain	1.0000
1:23313551:ACC:A	donor_loss	1.0000
1:23313552:C:CC	donor_gain	1.0000
1:23313552:C:CG	donor_loss	1.0000
1:23313698:TTTAC:T	acceptor_gain	1.0000
1:23313699:TTAC:T	acceptor_gain	1.0000
1:23313700:TAC:T	acceptor_gain	1.0000

AlphaMissense

4133 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:23310576:A:G	W594R	1.000
1:23310576:A:T	W594R	1.000
1:23310603:G:T	R585S	1.000
1:23310637:T:A	R573S	1.000
1:23310637:T:G	R573S	1.000
1:23310638:C:A	R573I	1.000
1:23310638:C:G	R573T	1.000
1:23311258:G:T	P411Q	1.000
1:23311259:G:A	P411S	1.000
1:23311260:C:A	K410N	1.000
1:23311260:C:G	K410N	1.000
1:23311262:T:C	K410E	1.000
1:23311264:G:A	A409V	1.000
1:23311264:G:T	A409D	1.000
1:23311265:C:T	A409T	1.000
1:23311273:A:C	I406R	1.000
1:23311273:A:T	I406K	1.000
1:23311321:G:T	A390D	1.000
1:23311322:C:G	A390P	1.000
1:23313560:G:T	A387D	1.000
1:23313568:T:A	R384S	1.000
1:23313568:T:G	R384S	1.000
1:23313569:C:A	R384I	1.000
1:23313569:C:G	R384T	1.000
1:23313577:A:C	F381L	1.000
1:23313577:A:T	F381L	1.000
1:23313578:A:G	F381S	1.000
1:23313579:A:G	F381L	1.000
1:23313579:A:T	F381I	1.000
1:23313580:A:C	H380Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000011953 (1:23343863 G>A,T), RS1000020640 (1:23337257 T>A,C), RS1000055644 (1:23343214 A>C), RS1000076889 (1:23337556 C>G), RS1000119317 (1:23324018 A>G), RS1000176590 (1:23322282 C>T), RS1000218722 (1:23305456 G>A), RS1000270947 (1:23313158 G>A), RS1000284889 (1:23314335 T>G), RS1000346223 (1:23326105 G>T), RS1000364510 (1:23343513 T>A,C,G), RS1000498698 (1:23326585 G>A,C,T), RS1000550897 (1:23305834 T>C), RS1000705454 (1:23332129 G>A), RS1000885330 (1:23326291 T>A,C)

Disease associations

OMIM: gene MIM:607201 | disease phenotypes: MIM:620073

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Mondo (2): neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities (MONDO:0859297), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Neurodevelopmental disorder-brain malformation-facial dysmorphism-brachydactyly syndrome (Orphanet:662189)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000066	Labial hypoplasia
HP:0000248	Brachycephaly
HP:0000347	Micrognathia
HP:0000431	Wide nasal bridge
HP:0000446	Narrow nasal bridge
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000506	Telecanthus
HP:0000540	Hypermetropia
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000733	Motor stereotypy
HP:0000826	Precocious puberty
HP:0000878	11 pairs of ribs
HP:0001007	Hirsutism
HP:0001156	Brachydactyly
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001320	Cerebellar vermis hypoplasia
HP:0001385	Hip dysplasia
HP:0001601	Laryngomalacia
HP:0001629	Ventricular septal defect
HP:0001773	Short foot
HP:0002079	Hypoplasia of the corpus callosum
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002650	Scoliosis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002394_128	Monocyte percentage of white cells	4.000000e-13
GCST90020028_521	Hip circumference adjusted for BMI	2.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067039 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.09	Kd	8.226	nM	CHEMBL5653589
8.09	ED50	8.226	nM	CHEMBL5653589
6.59	Kd	258.3	nM	CHEMBL3752910
6.59	ED50	258.3	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148537: Binding affinity to human HNRNPR incubated for 45 mins by Kinobead based pull down assay	kd	0.0082	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148537: Binding affinity to human HNRNPR incubated for 45 mins by Kinobead based pull down assay	kd	0.2583	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	8
bisphenol A	decreases expression, increases expression	3
cobaltous chloride	decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression, affects cotreatment	1
TAK-243	decreases sumoylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
trichostatin A	decreases expression	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
sodium arsenite	decreases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	affects expression	1
acyline	increases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bromovanin	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	increases expression, affects cotreatment	1
bisphenol AF	increases 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
CHEMBL5651579	Binding	Binding affinity to human HNRNPR 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

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2Z2	Abcam HEK293T HNRNPR KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice