R3HDM4

Summary

R3HDM4 (R3H domain containing 4, HGNC:28270) is a protein-coding gene on chromosome 19p13.3, encoding R3H domain-containing protein 4 (Q96D70).

Predicted to enable nucleic acid binding activity. Predicted to be located in nucleus.

Source: NCBI Gene 91300 — RefSeq curated summary.

At a glance

• GWAS associations: 36
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_138774

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28270
Approved symbol	R3HDM4
Name	R3H domain containing 4
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC16353
Ensembl gene	ENSG00000198858
Ensembl biotype	protein_coding
Entrez	91300

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000361574, ENST00000586080, ENST00000587975, ENST00000589428, ENST00000589445, ENST00000590454, ENST00000591829, ENST00000626716, ENST00000861805, ENST00000861806, ENST00000861807, ENST00000934479, ENST00000934480, ENST00000934481, ENST00000963825, ENST00000963826

RefSeq mRNA: 1 — MANE Select: NM_138774 NM_138774

CCDS: CCDS12048

Canonical transcript exons

ENST00000361574 — 8 exons

Exon	Start	End
ENSE00001211193	896503	897540
ENSE00002972025	913087	913219
ENSE00003493477	899440	899495
ENSE00003495790	901422	901546
ENSE00003510954	901976	902130
ENSE00003605100	900061	900146
ENSE00003609362	900829	900952
ENSE00003661178	899601	899686

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.5135 / max 2171.5794, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177951	45.5135	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.27	gold quality
secondary oocyte	CL:0000655	98.96	gold quality
oocyte	CL:0000023	98.46	gold quality
pancreatic ductal cell	CL:0002079	97.97	gold quality
lower esophagus mucosa	UBERON:0035834	97.94	gold quality
granulocyte	CL:0000094	97.74	gold quality
type B pancreatic cell	CL:0000169	97.65	gold quality
ileal mucosa	UBERON:0000331	97.25	gold quality
leukocyte	CL:0000738	97.18	gold quality
mononuclear cell	CL:0000842	97.10	gold quality
monocyte	CL:0000576	97.06	gold quality
olfactory bulb	UBERON:0002264	96.97	gold quality
spleen	UBERON:0002106	96.40	gold quality
bone marrow	UBERON:0002371	96.25	gold quality
periodontal ligament	UBERON:0008266	96.23	gold quality
trabecular bone tissue	UBERON:0002483	95.94	gold quality
esophagus mucosa	UBERON:0002469	95.70	gold quality
tibialis anterior	UBERON:0001385	95.33	gold quality
lymph node	UBERON:0000029	95.31	gold quality
thymus	UBERON:0002370	95.00	gold quality
nasal cavity epithelium	UBERON:0005384	94.94	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.70	gold quality
mucosa of urinary bladder	UBERON:0001259	94.67	gold quality
cartilage tissue	UBERON:0002418	94.65	gold quality
mammary duct	UBERON:0001765	94.59	gold quality
upper lobe of left lung	UBERON:0008952	94.53	gold quality
vena cava	UBERON:0004087	94.52	gold quality
amygdala	UBERON:0001876	94.36	gold quality
cardia of stomach	UBERON:0001162	94.31	gold quality
left uterine tube	UBERON:0001303	94.30	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	657.75
E-HCAD-10	no	2.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting R3HDM4, 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-4283	100.00	66.42	2097
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6815-3P	99.13	68.98	1530

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	r3hdm4	ENSDARG00000063254
mus_musculus	R3hdm4	ENSMUSG00000035781
rattus_norvegicus	R3hdm4	ENSRNOG00000011489
caenorhabditis_elegans		WBGENE00012908

Protein

Protein identifiers

R3H domain-containing protein 4 — Q96D70 (reviewed: Q96D70)

All UniProt accessions (4): Q96D70, K7EIG9, K7EN78, K7ER32

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

RefSeq proteins (1): NP_620129* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001374	R3H_dom	Domain
IPR025952	R3H-assoc_dom	Domain
IPR036867	R3H_dom_sf	Homologous_superfamily
IPR039629	R3HDM4	Family

Pfam: PF01424, PF13902

UniProt features (5 total): region of interest 2, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96D70-F1	77.37	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, RICKMAN_METASTASIS_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, MODULE_544, RICKMAN_TUMOR_DIFFERENTIATED_MODERATELY_VS_POORLY_UP, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, chr19p13, DODD_NASOPHARYNGEAL_CARCINOMA_DN, VERHAAK_GLIOBLASTOMA_CLASSICAL, JOHNSTONE_PARVB_TARGETS_3_UP, FOSTER_KDM1A_TARGETS_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MODULE_481, FOXN3_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): nucleic acid binding (GO:0003676)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2035 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
R3HDM4	FAM174C	Q9BVV8	476
R3HDM4	CIMAP1D	Q3SX64	474
R3HDM4	MIER2	Q8N344	446
R3HDM4	ARHGAP45	Q92619	445
R3HDM4	CMSS1	Q9BQ75	437
R3HDM4	SPMAP2	Q9P2T0	436
R3HDM4	MED16	Q9Y2X0	434
R3HDM4	TPGS1	Q6ZTW0	433
R3HDM4	C2CD4C	Q8TF44	431
R3HDM4	ATP5F1D	P30049	420
R3HDM4	ABR	Q12979	403
R3HDM4	DIRAS2	Q96HU8	399
R3HDM4	NSMF	Q6X4W1	394
R3HDM4	CBARP	Q8N350	393
R3HDM4	GALNT13	Q8IUC8	391

IntAct

4 interactions, top by confidence:

A	B	Type	Score
R3HDM4	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
R3HDM4	NPM1	psi-mi:“MI:0915”(physical association)	0.400
SLC15A3	GXYLT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): R3HDM4 (Affinity Capture-RNA), R3HDM4 (Proximity Label-MS), R3HDM4 (Proximity Label-MS), R3HDM4 (Affinity Capture-MS), FASN (Cross-Linking-MS (XL-MS)), R3HDM4 (Affinity Capture-MS), R3HDM4 (Affinity Capture-MS), R3HDM4 (Reconstituted Complex)

ESM2 similar proteins: A3KN19, A9JTG5, D3YWQ0, D3YY23, D4A615, D4ACP5, F1MAB7, O08580, O08722, O73916, O75427, O75912, O93307, O95475, P11474, P33279, P52824, P54274, P70371, Q08AE8, Q17RB8, Q1L5Z9, Q1L8G6, Q3U2C5, Q4TVR5, Q5QJV7, Q5RBA5, Q5U3H9, Q5U464, Q6NZL6, Q6QMY5, Q80ZX8, Q8BY98, Q8C0J6, Q8K1S6, Q8K2M3, Q8N594, Q8NC42, Q8R5G7, Q8TDY4

Diamond homologs: Q2KIL7, Q4VBF2, Q96D70

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1733 predictions. Top by Δscore:

Variant	Effect	Δscore
19:897554:C:CT	acceptor_gain	1.0000
19:897555:A:T	acceptor_gain	1.0000
19:899390:T:A	donor_gain	1.0000
19:899438:A:AC	donor_gain	1.0000
19:899438:ACTGG:A	donor_gain	1.0000
19:899439:C:CA	donor_gain	1.0000
19:899439:CTGG:C	donor_gain	1.0000
19:899439:CTGGC:C	donor_gain	1.0000
19:899496:C:CC	acceptor_gain	1.0000
19:899597:TTAC:T	donor_loss	1.0000
19:899600:C:A	donor_loss	1.0000
19:899687:C:CC	acceptor_gain	1.0000
19:899688:T:A	acceptor_loss	1.0000
19:900057:TCA:T	donor_loss	1.0000
19:900058:CACCA:C	donor_loss	1.0000
19:900059:A:AC	donor_gain	1.0000
19:900059:AC:A	donor_gain	1.0000
19:900060:C:CG	donor_gain	1.0000
19:900060:CC:C	donor_gain	1.0000
19:900060:CCA:C	donor_gain	1.0000
19:900060:CCAT:C	donor_gain	1.0000
19:900060:CCATG:C	donor_gain	1.0000
19:900142:GTCCT:G	acceptor_gain	1.0000
19:900143:TCCT:T	acceptor_gain	1.0000
19:900144:CCTC:C	acceptor_gain	1.0000
19:900145:CT:C	acceptor_gain	1.0000
19:900147:C:CC	acceptor_gain	1.0000
19:900150:C:CT	acceptor_gain	1.0000
19:900151:A:T	acceptor_gain	1.0000
19:900155:G:C	acceptor_gain	1.0000

AlphaMissense

1722 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:899451:A:G	L231P	0.999
19:899465:G:C	C226W	0.999
19:899466:C:T	C226Y	0.999
19:900949:A:G	W119R	0.999
19:900949:A:T	W119R	0.999
19:897507:A:T	V246D	0.998
19:899451:A:T	L231H	0.998
19:899461:A:C	Y228D	0.998
19:899467:A:G	C226R	0.998
19:899472:G:T	A224D	0.998
19:899476:G:C	H223D	0.998
19:900939:A:G	F122S	0.998
19:897485:G:C	F253L	0.997
19:897485:G:T	F253L	0.997
19:897487:A:G	F253L	0.997
19:899473:C:G	A224P	0.997
19:899484:A:G	L220P	0.997
19:899486:C:A	R219S	0.997
19:899486:C:G	R219S	0.997
19:899487:C:A	R219M	0.997
19:897465:A:T	L260Q	0.996
19:897486:A:G	F253S	0.996
19:899460:T:G	Y228S	0.996
19:899474:G:C	H223Q	0.996
19:899474:G:T	H223Q	0.996
19:899478:A:G	L222P	0.996
19:899481:A:G	L221P	0.996
19:899487:C:G	R219T	0.996
19:899461:A:G	Y228H	0.995
19:899461:A:T	Y228N	0.995

dbSNP variants (sampled 300 via entrez): RS1000006737 (19:906368 C>T), RS1000410056 (19:902636 A>C,G), RS1000417558 (19:898466 G>C), RS1000694695 (19:901642 T>C), RS1000752701 (19:897629 T>C,G), RS1000829934 (19:902079 G>A,C), RS1000880906 (19:902319 G>A), RS1001210775 (19:897749 C>T), RS1001220907 (19:907008 G>A,T), RS1001308787 (19:905207 CAA>C,CA,CAAA,CAAAAAAA,CAAAAAAAAA), RS1001324601 (19:907233 C>G,T), RS1001334364 (19:902402 G>A,C), RS1001395831 (19:902662 G>C), RS1001435409 (19:909853 A>T), RS1001655534 (19:913965 C>A,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST004611_141	High light scatter reticulocyte count	3.000000e-10
GCST004611_142	High light scatter reticulocyte count	3.000000e-22
GCST004611_143	High light scatter reticulocyte count	7.000000e-43
GCST004612_88	High light scatter reticulocyte percentage of red cells	1.000000e-10
GCST004612_89	High light scatter reticulocyte percentage of red cells	4.000000e-24
GCST004612_90	High light scatter reticulocyte percentage of red cells	5.000000e-42
GCST004619_206	Reticulocyte fraction of red cells	1.000000e-18
GCST004619_23	Reticulocyte fraction of red cells	1.000000e-10
GCST004619_93	Reticulocyte fraction of red cells	9.000000e-31
GCST004622_67	Reticulocyte count	8.000000e-10
GCST004622_68	Reticulocyte count	1.000000e-15
GCST004622_69	Reticulocyte count	4.000000e-31
GCST004628_29	Immature fraction of reticulocytes	1.000000e-18
GCST004628_30	Immature fraction of reticulocytes	2.000000e-37
GCST90002385_296	High light scatter reticulocyte count	2.000000e-62
GCST90002385_297	High light scatter reticulocyte count	2.000000e-29
GCST90002385_298	High light scatter reticulocyte count	2.000000e-62
GCST90002385_299	High light scatter reticulocyte count	1.000000e-09
GCST90002385_300	High light scatter reticulocyte count	2.000000e-99
GCST90002386_94	High light scatter reticulocyte percentage of red cells	1.000000e-44
GCST90002386_95	High light scatter reticulocyte percentage of red cells	6.000000e-25
GCST90002386_96	High light scatter reticulocyte percentage of red cells	4.000000e-11
GCST90002386_97	High light scatter reticulocyte percentage of red cells	1.000000e-54
GCST90002386_98	High light scatter reticulocyte percentage of red cells	1.000000e-107
GCST90002387_217	Immature fraction of reticulocytes	1.000000e-24
GCST90002387_218	Immature fraction of reticulocytes	2.000000e-13
GCST90002387_219	Immature fraction of reticulocytes	5.000000e-46
GCST90002387_220	Immature fraction of reticulocytes	3.000000e-73
GCST90002405_571	Reticulocyte count	5.000000e-39
GCST90002405_572	Reticulocyte count	2.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
Valproic Acid	affects expression, increases methylation	2
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
abrine	increases expression	1
Bortezomib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Ozone	affects expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	increases abundance, increases expression, affects cotreatment	1
Testosterone	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1
1-Butanol	increases abundance, increases expression, affects cotreatment	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

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