HNRNPH2

Summary

HNRNPH2 (heterogeneous nuclear ribonucleoprotein H2, HGNC:5042) is a protein-coding gene on chromosome Xq22.1, encoding Heterogeneous nuclear ribonucleoprotein H2 (P55795). This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm.

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 three repeats of quasi-RRM domains that binds to RNAs. It is very similar to the family member HNRPH1. This gene is thought to be involved in Fabray disease and X-linked agammaglobulinemia phenotype. Alternative splicing results in multiple transcript variants encoding the same protein. Read-through transcription between this locus and the ribosomal protein L36a gene has been observed.

Source: NCBI Gene 3188 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 72 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 52
• Druggable target: yes
• MANE Select transcript: NM_019597

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5042
Approved symbol	HNRNPH2
Name	heterogeneous nuclear ribonucleoprotein H2
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	hnRNPH’, FTP3, HNRPH'
Ensembl gene	ENSG00000126945
Ensembl biotype	protein_coding
OMIM	300610
Entrez	3188

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000316594, ENST00000867410, ENST00000867411, ENST00000867412, ENST00000867413, ENST00000918125, ENST00000942884, ENST00000942885, ENST00000942886, ENST00000942887

RefSeq mRNA: 2 — MANE Select: NM_019597 NM_001032393, NM_019597

CCDS: CCDS14485

Canonical transcript exons

ENST00000316594 — 2 exons

Exon	Start	End
ENSE00001458768	101408222	101408319
ENSE00001885873	101411936	101414133

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 100.9120 / max 2569.2970, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196953	96.9575	1821
196954	2.5744	1224
196956	0.7840	477
196955	0.5961	225

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	98.33	gold quality
islet of Langerhans	UBERON:0000006	98.23	gold quality
seminal vesicle	UBERON:0000998	97.67	gold quality
monocyte	CL:0000576	97.62	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.58	gold quality
mononuclear cell	CL:0000842	97.48	gold quality
leukocyte	CL:0000738	97.29	gold quality
palpebral conjunctiva	UBERON:0001812	97.15	gold quality
cortical plate	UBERON:0005343	97.07	gold quality
prefrontal cortex	UBERON:0000451	96.75	gold quality
ventricular zone	UBERON:0003053	96.73	gold quality
penis	UBERON:0000989	96.70	gold quality
endometrium	UBERON:0001295	96.69	gold quality
superficial temporal artery	UBERON:0001614	96.68	gold quality
esophagus squamous epithelium	UBERON:0006920	96.62	gold quality
ganglionic eminence	UBERON:0004023	96.49	gold quality
calcaneal tendon	UBERON:0003701	96.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.37	gold quality
pigmented layer of retina	UBERON:0001782	96.35	gold quality
rectum	UBERON:0001052	96.30	gold quality
germinal epithelium of ovary	UBERON:0001304	96.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.26	gold quality
right adrenal gland	UBERON:0001233	96.25	gold quality
jejunal mucosa	UBERON:0000399	96.24	gold quality
right adrenal gland cortex	UBERON:0035827	96.19	gold quality
left adrenal gland	UBERON:0001234	96.13	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.10	gold quality
jejunum	UBERON:0002115	96.08	gold quality
amniotic fluid	UBERON:0000173	96.07	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-3929	no	418.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting HNRNPH2, 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-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-337-3P	97.90	69.37	1052
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-383-5P	96.86	67.55	820
HSA-MIR-4436B-5P	96.71	68.37	1346
HSA-MIR-3654	96.43	66.55	646

Literature-anchored findings (GeneRIF, showing 10)

• the relative levels of hnRNP F and H2 in cells, as well as the target sequences in the downstream GRS on pre-mRNA, influence gene expression (PMID:16171461)
• altered function of hnRNP H1/H2 in tumor cells is a novel determinant of aberrant thymidine phosphorylase splicing thereby resulting in acquired chemoresistance to TP-activated fluoropyrimidine anticancer drugs. (PMID:21068389)
• Data indicate that armadillo repeat protein ARVCF interacts with the splicing factors the splicing factor SRSF1 (SF2/ASF), the RNA helicase p68 (DDX5), and the heterogeneous nuclear ribonucleoprotein hnRNP H2. (PMID:24644279)
• Results from a study on gene expression variability markers in early-stage human embryos shows that HNRNPH2 is a putative marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• identification of six females from independent families with a common neurodevelopmental phenotype including developmental delay, intellectual disability, autism, hypotonia, and seizures, all with de novo predicted deleterious variants in the nuclear localization signal of Heterogeneous Nuclear Ribonucleoprotein H2, encoded by HNRNPH2, a gene located on the X chromosome (PMID:27545675)
• Bain type of X-linked syndromic mental retardation in a male with a pathogenic variant in HNRNPH2. (PMID:31670473)
• Development and Pilot Screen of Novel High Content Assay for Down Regulators of Expression of Heterogenous Nuclear Ribonuclear Protein H2. (PMID:34014051)
• Variant-specific effects define the phenotypic spectrum of HNRNPH2-associated neurodevelopmental disorders in males. (PMID:34907471)
• Rett-like Phenotypes in HNRNPH2-Related Neurodevelopmental Disorder. (PMID:37372334)
• The RNA-binding proteins hnRNP H and F regulate splicing of a MYC-dependent HRAS exon in prostate cancer cells. (PMID:37399401)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hnrnph2	ENSMUSG00000045427
rattus_norvegicus	Hnrnph2	ENSRNOG00000011661

Paralogs (8): HNRNPH3 (ENSG00000096746), ESRP2 (ENSG00000103067), ESRP1 (ENSG00000104413), GRSF1 (ENSG00000132463), HNRNPH1 (ENSG00000169045), HNRNPF (ENSG00000169813), RBM12B (ENSG00000183808), RBM12 (ENSG00000244462)

Protein

Protein identifiers

Heterogeneous nuclear ribonucleoprotein H2 — P55795 (reviewed: P55795)

Alternative names: FTP-3, Heterogeneous nuclear ribonucleoprotein H'

All UniProt accessions (2): P55795, A0A384MDT2

UniProt curated annotations — full annotation on UniProt →

Function. This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Binds poly(RG).

Subunit / interactions. Component of a ribonucleoprotein complex containing mRNAs and RNA-binding proteins including DDX5, HNRNPH2 and SRSF1 as well as splicing regulator ARVCF. Interacts with TXNL4/DIM1.

Subcellular location. Nucleus. Nucleoplasm.

Tissue specificity. Expressed ubiquitously.

Disease relevance. Intellectual developmental disorder, X-linked, syndromic, Bain type (MRXSB) [MIM:300986] A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSB patients manifest developmental delay, intellectual disability, autism, hypotonia, seizures, and dysmorphic facial features. Only females are affected. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_001027565, NP_062543* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR012996	Znf_CHHC	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050666	ESRP	Family

Pfam: PF00076, PF08080

UniProt features (49 total): strand 14, modified residue 10, helix 4, repeat 4, cross-link 3, sequence variant 3, domain 3, turn 3, chain 2, region of interest 2, initiator methionine 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8SGH	ELECTRON MICROSCOPY	3.17
1WEZ	SOLUTION NMR
1WG5	SOLUTION NMR
6DG1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55795-F1	62.24	0.00

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 (13): 1, 2, 23, 54, 63, 90, 233, 233, 246, 310, 35, 87, 98

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: 259 (showing top): GGGTGGRR_PAX4_03, EFC_Q6, PAX2_01, MORF_RAF1, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, USF_01, GOBP_RNA_SPLICING, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, REACTOME_MRNA_SPLICING, SCHLOSSER_SERUM_RESPONSE_DN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, NKX22_01, MODULE_98

GO Biological Process (1): regulation of RNA splicing (GO:0043484)

GO Molecular Function (3): RNA binding (GO:0003723), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), membrane (GO:0016020), ribonucleoprotein complex (GO:1990904)

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
cellular anatomical structure	3
binding	2
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
protein-containing complex	1

Protein interactions and networks

STRING

1514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HNRNPH2	HNRNPM	P52272	919
HNRNPH2	SRSF2	Q01130	857
HNRNPH2	ILF2	Q12905	841
HNRNPH2	ILF3	Q12906	832
HNRNPH2	HNRNPA1	P09651	824
HNRNPH2	MATR3	P43243	814
HNRNPH2	HNRNPU	Q00839	772
HNRNPH2	CELF1	Q92879	770
HNRNPH2	DDX5	P17844	767
HNRNPH2	HNRNPC	P07910	760
HNRNPH2	SRSF1	Q07955	758
HNRNPH2	HNRNPA3	P51991	746
HNRNPH2	MBNL1	Q9NR56	745
HNRNPH2	C9orf72	Q96LT7	724
HNRNPH2	PTBP1	P26599	712

IntAct

171 interactions, top by confidence:

A	B	Type	Score
HNRNPH2	TEKT1	psi-mi:“MI:0915”(physical association)	0.720
MSI2	HNRNPH2	psi-mi:“MI:0915”(physical association)	0.720
TEKT1	HNRNPH2	psi-mi:“MI:0915”(physical association)	0.720
HNRNPH2	MSI2	psi-mi:“MI:0915”(physical association)	0.720
HNRNPH2	PLOD1	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ERBB3	PIK3R2	psi-mi:“MI:0914”(association)	0.700
UBASH3B	EGFR	psi-mi:“MI:0914”(association)	0.690
STAMBPL1	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
MSI1	HNRNPH2	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	HNRNPH2	psi-mi:“MI:0915”(physical association)	0.560
CCNK	HNRNPH2	psi-mi:“MI:0915”(physical association)	0.560
Zfp36	CNOT1	psi-mi:“MI:0914”(association)	0.560
HNRNPH2	HNRNPA0	psi-mi:“MI:0915”(physical association)	0.550
HNRNPH2	PLOD2	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
NAGK	ZBTB43	psi-mi:“MI:0914”(association)	0.530
PLOD3	COL4A1	psi-mi:“MI:0914”(association)	0.530
ERBB2	NDUFA4	psi-mi:“MI:0914”(association)	0.530
HNRNPH2	TLE5	psi-mi:“MI:0915”(physical association)	0.490

BioGRID (388): TEKT1 (Two-hybrid), MSI2 (Two-hybrid), HNRNPH2 (Affinity Capture-MS), HNRNPH2 (Affinity Capture-MS), HNRNPH2 (Affinity Capture-MS), HNRNPH2 (Affinity Capture-MS), HNRNPH2 (Affinity Capture-MS), HNRNPH2 (Two-hybrid), HNRNPH1 (Co-fractionation), HNRNPH2 (Co-fractionation), HNRNPH2 (Co-fractionation), HNRNPH2 (Co-fractionation), HNRNPH2 (Co-fractionation), HNRNPH2 (Co-fractionation), HNRNPH2 (Co-fractionation)

ESM2 similar proteins: B2GV05, B5FXN8, G3V9R8, O08583, O75525, O77768, P07910, P19600, P23588, P52756, P55795, P70333, P97379, P97855, Q08DJ0, Q0VFL7, Q13148, Q13283, Q1RMU5, Q28FB9, Q32LC7, Q3SZF3, Q3T0I4, Q58EA2, Q5R5W2, Q5R9L3, Q5RA82, Q5RB87, Q5RD26, Q5SRX1, Q5VWX1, Q5ZLN5, Q60HC3, Q64012, Q6AY09, Q6GLW1, Q86SE5, Q86V81, Q8BGD9, Q8BTF8

Diamond homologs: A1L1G1, A8WPC5, B2RYD2, B2RYJ8, O35737, P31943, P52597, P55795, P70333, Q12849, Q22708, Q3SZF3, Q3US41, Q5E9J1, Q5RD26, Q5ZLR4, Q60HC3, Q6AY09, Q6DEZ7, Q6NXG1, Q794E4, Q7ZVR8, Q7ZY29, Q8C5Q4, Q8K0G8, Q8R3C6, Q8VHV7, Q9BJZ5, Q9H6T0, Q9Z2X1, P31942, Q9Y4C8, Q15020, Q5REG1, Q9JLI8, Q5RBM8, Q8R4X3, Q8SQ27, Q9NTZ6, Q66JV4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HNRNPH2	“down-regulates quantity”	TERF2	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 168 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 3’-end processing	6	10.2×	3e-03
Signaling by ALK fusions and activated point mutants	7	9.1×	2e-03
mRNA Splicing - Major Pathway	16	7.5×	2e-07
mRNA Polyadenylation	9	6.8×	2e-03
Processing of Capped Intron-Containing Pre-mRNA	8	5.7×	7e-03
PIP3 activates AKT signaling	9	5.2×	6e-03
Dengue Virus-Host Interactions	12	4.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of translation	12	16.7×	4e-09
mRNA stabilization	6	15.6×	4e-04
autophagosome maturation	6	14.9×	5e-04
regulation of alternative mRNA splicing, via spliceosome	8	13.9×	3e-05
mitophagy	5	11.3×	6e-03
mRNA splicing, via spliceosome	17	11.0×	3e-10
phosphatidylinositol 3-kinase/protein kinase B signal transduction	7	10.5×	6e-04
RNA splicing	9	5.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	44
Likely benign	19
Benign	0

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
225761	NM_019597.5(HNRNPH2):c.617G>A (p.Arg206Gln)	Pathogenic
3600632	NM_019597.5(HNRNPH2):c.623G>T (p.Gly208Val)	Pathogenic
4076608	NM_019597.5(HNRNPH2):c.634A>G (p.Arg212Gly)	Pathogenic
451161	NM_019597.5(HNRNPH2):c.573del (p.Arg192fs)	Pathogenic
1708044	NM_019597.5(HNRNPH2):c.613C>T (p.Gln205Ter)	Likely pathogenic
1708226	NM_019597.5(HNRNPH2):c.460del (p.Glu154fs)	Likely pathogenic
2577964	NM_019597.5(HNRNPH2):c.636G>T (p.Arg212Ser)	Likely pathogenic

SpliceAI

288 predictions. Top by Δscore:

Variant	Effect	Δscore
X:101411932:TCA:T	acceptor_loss	1.0000
X:101411933:CAG:C	acceptor_loss	1.0000
X:101411934:A:AG	acceptor_gain	1.0000
X:101411935:G:GA	acceptor_gain	1.0000
X:101411935:G:GG	acceptor_gain	1.0000
X:101411935:GC:G	acceptor_gain	1.0000
X:101411935:GCT:G	acceptor_gain	1.0000
X:101411935:GCTA:G	acceptor_gain	1.0000
X:101411935:GCTAC:G	acceptor_gain	1.0000
X:101411931:TTCA:T	acceptor_loss	0.9900
X:101411934:AG:A	acceptor_loss	0.9900
X:101408286:G:T	donor_gain	0.9600
X:101408515:GT:G	donor_gain	0.9500
X:101408286:G:GT	donor_gain	0.9400
X:101408315:TAGAG:T	donor_loss	0.9300
X:101408319:GGTT:G	donor_loss	0.9300
X:101408320:GTTG:G	donor_loss	0.9300
X:101408321:T:G	donor_loss	0.9300
X:101408517:G:GG	donor_gain	0.9200
X:101408293:G:GT	donor_gain	0.9000
X:101408297:A:T	donor_gain	0.8600
X:101408613:T:G	donor_gain	0.8600
X:101408318:AGGTT:A	donor_gain	0.8500
X:101408220:T:G	donor_gain	0.8000
X:101408296:G:GT	donor_gain	0.8000
X:101408605:GCCC:G	donor_gain	0.8000
X:101408243:T:TA	donor_gain	0.7900
X:101408244:A:AA	donor_gain	0.7900
X:101408323:G:GC	donor_loss	0.7800
X:101408324:GTGT:G	donor_loss	0.7700

AlphaMissense

2979 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:101412035:G:T	R16M	1.000
X:101412037:G:C	G17R	1.000
X:101412037:G:T	G17C	1.000
X:101412038:G:A	G17D	1.000
X:101412038:G:T	G17V	1.000
X:101412041:T:C	L18P	1.000
X:101412046:T:A	W20R	1.000
X:101412046:T:C	W20R	1.000
X:101412048:G:C	W20C	1.000
X:101412048:G:T	W20C	1.000
X:101412151:G:C	G55R	1.000
X:101412151:G:T	G55C	1.000
X:101412152:G:A	G55D	1.000
X:101412152:G:T	G55V	1.000
X:101412157:G:C	A57P	1.000
X:101412164:T:A	V59D	1.000
X:101412230:G:C	R81T	1.000
X:101412230:G:T	R81I	1.000
X:101412231:A:C	R81S	1.000
X:101412231:A:T	R81S	1.000
X:101412232:T:C	Y82H	1.000
X:101412236:T:A	V83D	1.000
X:101412244:T:C	F86L	1.000
X:101412246:C:A	F86L	1.000
X:101412246:C:G	F86L	1.000
X:101412326:T:A	V113D	1.000
X:101412332:T:A	L115H	1.000
X:101412332:T:C	L115P	1.000
X:101412335:G:C	R116T	1.000
X:101412335:G:T	R116I	1.000

dbSNP variants (sampled 300 via entrez): RS1000333260 (X:101408605 G>A), RS1000623276 (X:101407125 C>T), RS1000685069 (X:101408911 C>T), RS1001078239 (X:101406427 C>G), RS1001460927 (X:101408174 G>A,T), RS1004138902 (X:101414193 A>G), RS1004802201 (X:101407663 C>G), RS1008140134 (X:101411570 C>T), RS1008531323 (X:101408988 C>A), RS1009215236 (X:101406367 G>T), RS1011494141 (X:101410543 T>C), RS1012228073 (X:101414529 T>C), RS1012280506 (X:101411932 T>C), RS1012558563 (X:101410431 G>A), RS1014289130 (X:101408227 C>G,T)

Disease associations

OMIM: gene MIM:300610 | disease phenotypes: MIM:300986

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, X-linked, syndromic, Bain type	Strong	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
X-linked complex neurodevelopmental disorder	Definitive	XL

Mondo (3): intellectual disability, X-linked, syndromic, Bain type (MONDO:0010512), stereotypic movement disorder (MONDO:0002265), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Neurodevelopmental delay-intellectual disability-skeletal defects syndrome (Orphanet:662198)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000154	Wide mouth
HP:0000218	High palate
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000347	Micrognathia
HP:0000430	Underdeveloped nasal alae
HP:0000577	Exotropia
HP:0000601	Hypotelorism
HP:0000718	Aggressive behavior
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000739	Anxiety
HP:0000768	Pectus carinatum
HP:0001166	Arachnodactyly
HP:0001212	Prominent fingertip pads
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001321	Cerebellar hypoplasia
HP:0001344	Absent speech
HP:0001382	Joint hypermobility
HP:0001423	X-linked dominant inheritance
HP:0001508	Failure to thrive
HP:0001631	Atrial septal defect

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
D019956	Stereotypic Movement Disorder	F03.625.984

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296005 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs869312136	Efficacy	3	migalastat	Fabry Disease
rs869312138	Efficacy	3	migalastat	Fabry Disease

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs869312136	GLA, HNRNPH2	3	0.00	1	migalastat
rs869312138	GLA, HNRNPH2	3	0.00	1	migalastat

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Cadmium	increases abundance, increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
kojic acid	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
cupric oxide	increases expression	1
resorcinol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
bromovanin	decreases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	decreases phosphorylation	1
Catechin	affects cotreatment, increases expression	1
Chromium	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118565	Binding	Binding affinity to HNRNPH2 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B3SK	SMCPGi001-A	Induced pluripotent stem cell	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