R3HDM1

Summary

R3HDM1 (R3H domain containing 1, HGNC:9757) is a protein-coding gene on chromosome 2q21.3, encoding R3H domain-containing protein 1 (Q15032).

Enables RNA binding activity.

Source: NCBI Gene 23518 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 149 total
• MANE Select transcript: NM_001378107

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9757
Approved symbol	R3HDM1
Name	R3H domain containing 1
Location	2q21.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0029
Ensembl gene	ENSG00000048991
Ensembl biotype	protein_coding
OMIM	619474
Entrez	23518

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 32 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000264160, ENST00000409478, ENST00000409606, ENST00000410054, ENST00000425804, ENST00000436436, ENST00000438014, ENST00000441871, ENST00000443537, ENST00000445855, ENST00000456040, ENST00000463230, ENST00000480793, ENST00000483021, ENST00000483065, ENST00000486532, ENST00000487294, ENST00000488035, ENST00000628915, ENST00000683871, ENST00000869753, ENST00000869754, ENST00000869755, ENST00000869756, ENST00000869757, ENST00000869758, ENST00000869759, ENST00000940057, ENST00000940058, ENST00000940059, ENST00000940060, ENST00000940061, ENST00000940062, ENST00000940063, ENST00000940064, ENST00000940065, ENST00000940066, ENST00000964911, ENST00000964912, ENST00000964913

RefSeq mRNA: 7 — MANE Select: NM_001378107 NM_001282798, NM_001282799, NM_001282800, NM_001354199, NM_001354200, NM_001378107, NM_015361

CCDS: CCDS2177, CCDS63024, CCDS63025, CCDS63026, CCDS92870

Canonical transcript exons

ENST00000683871 — 27 exons

Exon	Start	End
ENSE00000527676	135661270	135661393
ENSE00000964081	135675332	135675486
ENSE00000964082	135680173	135680324
ENSE00000964083	135709433	135709536
ENSE00001297524	135616668	135616757
ENSE00001314494	135641536	135641790
ENSE00001314818	135616152	135616193
ENSE00001321432	135604806	135605016
ENSE00001588598	135651730	135652032
ENSE00001705767	135710059	135710231
ENSE00001726888	135722469	135722553
ENSE00001731988	135649902	135650003
ENSE00001741091	135715550	135715694
ENSE00003477409	135631718	135631777
ENSE00003485847	135602500	135602708
ENSE00003487278	135621494	135621608
ENSE00003576795	135721924	135722006
ENSE00003632503	135635890	135635998
ENSE00003652578	135638618	135638655
ENSE00003659574	135638739	135638789
ENSE00003677503	135631861	135632001
ENSE00003678169	135622654	135622732
ENSE00003685935	135645379	135645527
ENSE00003692789	135638896	135639122
ENSE00003789883	135636088	135636183
ENSE00003920092	135531484	135531633
ENSE00003921923	135723937	135725269

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.4126 / max 2153.0421, expressed in 1796 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22643	16.4256	1796
22646	4.8256	97
22647	0.4805	59
22645	0.4627	53
22644	0.2183	107

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	98.55	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.06	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.97	gold quality
frontal pole	UBERON:0002795	97.67	gold quality
primary visual cortex	UBERON:0002436	97.66	gold quality
occipital lobe	UBERON:0002021	97.64	gold quality
superior frontal gyrus	UBERON:0002661	96.68	gold quality
orbitofrontal cortex	UBERON:0004167	96.50	gold quality
sperm	CL:0000019	96.33	gold quality
cortical plate	UBERON:0005343	96.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.97	gold quality
parietal lobe	UBERON:0001872	95.81	gold quality
right frontal lobe	UBERON:0002810	95.77	gold quality
frontal cortex	UBERON:0001870	95.73	gold quality
frontal lobe	UBERON:0016525	95.73	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.67	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.59	gold quality
endothelial cell	CL:0000115	95.39	gold quality
neocortex	UBERON:0001950	95.38	gold quality
prefrontal cortex	UBERON:0000451	95.37	gold quality
entorhinal cortex	UBERON:0002728	95.35	gold quality
postcentral gyrus	UBERON:0002581	95.32	gold quality
colonic epithelium	UBERON:0000397	95.25	gold quality
male germ cell	CL:0000015	95.03	gold quality
cerebral cortex	UBERON:0000956	94.71	gold quality
corpus callosum	UBERON:0002336	94.29	gold quality
gluteal muscle	UBERON:0002000	93.94	gold quality
CA1 field of hippocampus	UBERON:0003881	93.91	gold quality
cingulate cortex	UBERON:0003027	93.87	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	1973.85
E-HCAD-35	yes	106.63
E-ANND-3	yes	5.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting R3HDM1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836

Literature-anchored findings (GeneRIF, showing 1)

• R3HDM1 haploinsufficiency is associated with mild intellectual disability. (PMID:33750005)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	r3hdm1	ENSDARG00000101458
mus_musculus	R3hdm1	ENSMUSG00000056211
rattus_norvegicus	R3hdm1	ENSRNOG00000004099

Paralogs (2): ARPP21 (ENSG00000172995), R3HDM2 (ENSG00000179912)

Protein

Protein identifiers

R3H domain-containing protein 1 — Q15032 (reviewed: Q15032)

All UniProt accessions (8): A0A804HIA8, C9JIX1, Q15032, C9JIX3, H7BZ47, H7C1X4, H7C2F9, H7C3T7

UniProt curated annotations — full annotation on UniProt →

Isoforms (4)

UniProt ID	Names	Canonical?
Q15032-1	1	yes
Q15032-2	2
Q15032-3	3
Q15032-4	4

RefSeq proteins (7): NP_001269727, NP_001269728, NP_001269729, NP_001341128, NP_001341129, NP_001365036, NP_056176 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001374	R3H_dom	Domain
IPR024771	SUZ	Domain
IPR036867	R3H_dom_sf	Homologous_superfamily
IPR051937	R3H_domain_containing	Family

Pfam: PF01424, PF12752

UniProt features (38 total): modified residue 9, region of interest 8, compositionally biased region 8, splice variant 5, sequence conflict 3, domain 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15032-F1	49.29	0.09

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 (9): 187, 262, 302, 380, 381, 393, 929, 929, 973

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 242 (showing top): RNGTGGGC_UNKNOWN, FXR_IR1_Q6, MORF_DNMT1, MORF_SMC1L1, TGCACTT_MIR519C_MIR519B_MIR519A, WANG_RECURRENT_LIVER_CANCER_UP, MORF_RRM1, MORF_HDAC1, MORF_HDAC2, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, AACWWCAANK_UNKNOWN, CATTTCA_MIR203, MODULE_195, AAACCAC_MIR140

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
nucleic acid binding	1

Protein interactions and networks

STRING

986 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
R3HDM1	UBXN4	Q92575	522
R3HDM1	ZRANB3	Q5FWF4	512
R3HDM1	RAB3GAP1	Q15042	460
R3HDM1	NPIPB6	E9PJ23	447
R3HDM1	MAPK7	Q13164	391
R3HDM1	COPZ2	Q9P299	387
R3HDM1	ABCG2	Q9UNQ0	383
R3HDM1	WDR55	Q9H6Y2	374
R3HDM1	GTF3C3	Q9Y5Q9	371
R3HDM1	CDHR4	A6H8M9	364
R3HDM1	OR9Q2	Q8NGE9	358
R3HDM1	OOSP1	A8MZH6	357
R3HDM1	ABHD17C	Q6PCB6	348
R3HDM1	GHR	P10912	338
R3HDM1	ELP5	Q8TE02	335

IntAct

52 interactions, top by confidence:

A	B	Type	Score
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
R3HDM1	F2RL1	psi-mi:“MI:0915”(physical association)	0.370
R3HDM1	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
rep	ZNF609	psi-mi:“MI:0914”(association)	0.350
YWHAQ	MCRIP1	psi-mi:“MI:0914”(association)	0.350
YWHAB	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAG	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAH	BRAF	psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350

BioGRID (120): R3HDM1 (Proximity Label-MS), R3HDM1 (Affinity Capture-MS), R3HDM1 (Affinity Capture-MS), R3HDM1 (Affinity Capture-MS), R3HDM1 (Affinity Capture-MS), R3HDM1 (Affinity Capture-MS), R3HDM1 (Affinity Capture-MS), R3HDM1 (Affinity Capture-RNA), R3HDM1 (Affinity Capture-MS), R3HDM1 (Synthetic Lethality), R3HDM1 (Proximity Label-MS), R3HDM1 (Proximity Label-MS), R3HDM1 (Proximity Label-MS), R3HDM1 (Proximity Label-MS), R3HDM1 (Proximity Label-MS)

ESM2 similar proteins: A0A0G2JTY4, A0JNC2, A2AQ25, E1BEQ5, O09000, O57539, O70305, O93602, P15336, P16951, P17544, P70365, P97305, Q00969, Q02930, Q12968, Q14157, Q15032, Q15596, Q15788, Q1LY51, Q4PJW2, Q4VCS5, Q5R9C9, Q5SFM8, Q5T5P2, Q5T6F2, Q61026, Q62415, Q6GP15, Q80TM6, Q80X50, Q86YP4, Q8CHY6, Q8IY63, Q8VCB2, Q8VHG2, Q8VHR5, Q8WXI9, Q91VX2

Diamond homologs: A0JNC2, Q15032, Q80TM6, Q8MSX1, Q9DCB4, Q9UBL0, Q9Y2K5, Q5R6X9, Q7M2N1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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
Activation of BAD and translocation to mitochondria	6	130.5×	3e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	115.2×	4e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	115.2×	4e-10
Activation of BH3-only proteins	6	85.1×	3e-09
RHO GTPases activate PKNs	6	54.4×	3e-08
Intrinsic Pathway for Apoptosis	6	50.2×	5e-08
SARS-CoV-1-host interactions	7	35.1×	3e-08
Programmed Cell Death	7	29.3×	8e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	38.2×	8e-05
intracellular protein localization	6	13.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5163 predictions. Top by Δscore:

Variant	Effect	Δscore
2:135602493:A:AG	acceptor_gain	1.0000
2:135602494:T:G	acceptor_gain	1.0000
2:135602495:TTTA:T	acceptor_loss	1.0000
2:135602496:TTAG:T	acceptor_loss	1.0000
2:135602496:TTAGG:T	acceptor_gain	1.0000
2:135602497:TA:T	acceptor_loss	1.0000
2:135602497:TAG:T	acceptor_gain	1.0000
2:135602498:A:AG	acceptor_gain	1.0000
2:135602498:AG:A	acceptor_gain	1.0000
2:135602498:AGG:A	acceptor_gain	1.0000
2:135602498:AGGCC:A	acceptor_loss	1.0000
2:135602499:G:GC	acceptor_gain	1.0000
2:135602499:GG:G	acceptor_gain	1.0000
2:135602499:GGC:G	acceptor_gain	1.0000
2:135602499:GGCC:G	acceptor_gain	1.0000
2:135602499:GGCCA:G	acceptor_gain	1.0000
2:135602704:ATCAG:A	donor_loss	1.0000
2:135602705:TCAGG:T	donor_loss	1.0000
2:135602706:CAGG:C	donor_loss	1.0000
2:135602707:AGGT:A	donor_loss	1.0000
2:135602708:GG:G	donor_loss	1.0000
2:135602709:G:A	donor_loss	1.0000
2:135602710:T:G	donor_loss	1.0000
2:135604804:A:G	acceptor_gain	1.0000
2:135616666:A:AG	acceptor_gain	1.0000
2:135616667:G:GG	acceptor_gain	1.0000
2:135616667:GTCAA:G	acceptor_gain	1.0000
2:135621492:A:AG	acceptor_gain	1.0000
2:135621493:G:GG	acceptor_gain	1.0000
2:135621493:GGA:G	acceptor_gain	1.0000

AlphaMissense

7440 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:135622674:G:C	D147H	1.000
2:135622675:A:T	D147V	1.000
2:135622693:T:C	L153P	1.000
2:135622701:T:C	F156L	1.000
2:135622702:T:C	F156S	1.000
2:135622702:T:G	F156C	1.000
2:135622703:T:A	F156L	1.000
2:135622703:T:G	F156L	1.000
2:135622705:T:C	L157S	1.000
2:135622717:T:C	L161S	1.000
2:135631719:G:C	D167H	1.000
2:135631720:A:C	D167A	1.000
2:135631720:A:G	D167G	1.000
2:135631720:A:T	D167V	1.000
2:135631732:T:A	L171Q	1.000
2:135631732:T:C	L171P	1.000
2:135631732:T:G	L171R	1.000
2:135631744:A:T	E175V	1.000
2:135631878:T:C	F192S	1.000
2:135631895:T:C	Y198H	1.000
2:135631895:T:G	Y198D	1.000
2:135631896:A:G	Y198C	1.000
2:135631901:A:T	R200W	1.000
2:135631902:G:C	R200T	1.000
2:135631902:G:T	R200M	1.000
2:135631903:G:C	R200S	1.000
2:135631903:G:T	R200S	1.000
2:135631905:T:C	M201T	1.000
2:135631905:T:G	M201R	1.000
2:135631906:G:A	M201I	1.000

dbSNP variants (sampled 300 via entrez): RS1000005411 (2:135560066 G>T), RS1000021051 (2:135599404 T>C), RS1000036369 (2:135687230 A>G), RS1000049869 (2:135708626 G>A,T), RS1000084784 (2:135531610 GCCT>G,GCCTCCT), RS1000090996 (2:135640601 A>G,T), RS1000093943 (2:135592467 G>A), RS1000109440 (2:135655143 G>T), RS1000116469 (2:135659676 G>A), RS1000123192 (2:135592647 G>T), RS1000132064 (2:135582801 GC>G), RS1000147984 (2:135654307 A>ACT), RS1000173353 (2:135682357 A>G), RS1000195574 (2:135707874 T>C), RS1000212661 (2:135565350 A>G)

Disease associations

OMIM: gene MIM:619474 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004863_61	Mosquito bite size	2.000000e-10
GCST005829_25	Hand grip strength	3.000000e-09
GCST005830_96	Hand grip strength	2.000000e-12
GCST005951_43	Body mass index	5.000000e-09
GCST005951_44	Body mass index	1.000000e-09
GCST007576_42	Chronotype	5.000000e-09
GCST008334_1	Neutrophil count	8.000000e-12
GCST008839_297	Height	1.000000e-11
GCST010241_32	Apolipoprotein A1 levels	1.000000e-16
GCST010242_50	HDL cholesterol levels	1.000000e-14
GCST90002404_24	Red cell distribution width	8.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0008378	mosquito bite reaction size measurement
EFO:0006941	grip strength measurement
EFO:0004340	body mass index
EFO:0008328	chronotype measurement
EFO:0004833	neutrophil count
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Valproic Acid	affects expression, decreases methylation	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
arsenite	affects binding, decreases reaction	1
coumarin	increases phosphorylation	1
ICG 001	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Phthalic Acids	decreases methylation	1
Ribonucleotides	affects binding	1
Selenium	decreases expression	1
Tretinoin	decreases expression	1
Vitamin E	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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