R3HCC1

Summary

R3HCC1 (R3H domain and coiled-coil containing 1, HGNC:27329) is a protein-coding gene on chromosome 8p21.3, encoding R3H and coiled-coil domain-containing protein 1 (Q9Y3T6).

Predicted to enable nucleic acid binding activity.

Source: NCBI Gene 203069 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_001136108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27329
Approved symbol	R3HCC1
Name	R3H domain and coiled-coil containing 1
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp564N123
Ensembl gene	ENSG00000104679
Ensembl biotype	protein_coding
Entrez	203069

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000265806, ENST00000411463, ENST00000517633, ENST00000518840, ENST00000519952, ENST00000520480, ENST00000521588, ENST00000522012, ENST00000523720, ENST00000625275

RefSeq mRNA: 2 — MANE Select: NM_001136108 NM_001136108, NM_001301650

CCDS: CCDS47826, CCDS78317

Canonical transcript exons

ENST00000265806 — 8 exons

Exon	Start	End
ENSE00002138933	23295967	23296279
ENSE00003515218	23289016	23289153
ENSE00003562417	23293303	23293373
ENSE00003577968	23289866	23290469
ENSE00003591496	23291361	23291533
ENSE00003660630	23294769	23294864
ENSE00003774169	23288506	23288633
ENSE00003841636	23288108	23288157

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 95.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.2326 / max 124.0650, expressed in 1806 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87893	16.0523	1806
87890	0.1157	35
87889	0.0425	24
87891	0.0221	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	95.90	gold quality
spinal cord	UBERON:0002240	95.33	gold quality
parotid gland	UBERON:0001831	95.24	gold quality
inferior vagus X ganglion	UBERON:0005363	94.40	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.32	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.77	gold quality
body of pancreas	UBERON:0001150	93.24	gold quality
substantia nigra pars compacta	UBERON:0001965	93.23	gold quality
pons	UBERON:0000988	93.20	gold quality
gluteal muscle	UBERON:0002000	93.14	gold quality
substantia nigra	UBERON:0002038	93.03	gold quality
midbrain	UBERON:0001891	92.95	gold quality
triceps brachii	UBERON:0001509	92.92	gold quality
subthalamic nucleus	UBERON:0001906	92.88	gold quality
middle frontal gyrus	UBERON:0002702	92.86	gold quality
dorsal plus ventral thalamus	UBERON:0001897	92.72	gold quality
lateral globus pallidus	UBERON:0002476	92.70	gold quality
apex of heart	UBERON:0002098	92.53	gold quality
prefrontal cortex	UBERON:0000451	92.48	gold quality
inferior olivary complex	UBERON:0002127	92.45	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.27	gold quality
lower esophagus	UBERON:0013473	92.24	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.13	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.03	gold quality
type B pancreatic cell	CL:0000169	92.00	silver quality
paraflocculus	UBERON:0005351	91.96	gold quality
cranial nerve II	UBERON:0000941	91.94	gold quality
olfactory bulb	UBERON:0002264	91.92	silver quality
body of stomach	UBERON:0001161	91.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.40
E-MTAB-7303	no	1057.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting R3HCC1, 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-4673	100.00	66.64	1490
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980
HSA-MIR-4314	97.50	67.30	1369

Literature-anchored findings (GeneRIF, showing 2)

• Ribosome profiling indicates that this gene can use a non-AUG (CUG) start codon in both human HEK293 and mouse embryonic fibroblast cells. (PMID:22927429)
• Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity. (PMID:36308049)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	r3hcc1	ENSDARG00000099593
mus_musculus	R3hcc1	ENSMUSG00000034194
rattus_norvegicus	R3hcc1	ENSRNOG00000016777
drosophila_melanogaster	CG2162	FBGN0035388
caenorhabditis_elegans		WBGENE00008622

Paralogs (1): R3HCC1L (ENSG00000166024)

Protein

Protein identifiers

R3H and coiled-coil domain-containing protein 1 — Q9Y3T6 (reviewed: Q9Y3T6)

All UniProt accessions (10): A0A0D9SF44, A0A0D9SFI4, A0A0D9SG39, A0A0R4J2E2, A0A7P0N5L0, E5RHX3, E5RIK1, E5RIQ4, Q9Y3T6, H0YBU3

UniProt curated annotations — full annotation on UniProt →

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y3T6-1	1	yes
Q9Y3T6-3	2

RefSeq proteins (2): NP_001129580, NP_001288579 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001374	R3H_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR036867	R3H_dom_sf	Homologous_superfamily
IPR039884	R3HC1/R3HCL	Family

Pfam: PF01424

UniProt features (13 total): sequence variant 4, region of interest 2, compositionally biased region 2, chain 1, domain 1, coiled-coil region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3T6-F1	66.87	0.28

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 (1): 236

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): chr8p21, YOSHIMURA_MAPK8_TARGETS_UP, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_2H_DN, CBX5_TARGET_GENES, SNIP1_TARGET_GENES, SUPT16H_TARGET_GENES, TEAD2_TARGET_GENES, ZNF213_TARGET_GENES, ZNF30_TARGET_GENES, ZNF391_TARGET_GENES, ZNF423_TARGET_GENES, ZNF513_TARGET_GENES, ZNF524_TARGET_GENES, ZNF561_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
R3HCC1	CHMP7	Q8WUX9	518
R3HCC1	SVOPL	Q8N434	510
R3HCC1	FAM149A	A5PLN7	439
R3HCC1	MOCS1	Q9NZB8	434
R3HCC1	TMEM63C	Q9P1W3	428
R3HCC1	ZNF414	Q96IQ9	421
R3HCC1	YIPF3	Q9GZM5	421
R3HCC1	PAPLN	O95428	416
R3HCC1	DDX55	Q8NHQ9	411
R3HCC1	FAM124A	Q86V42	399
R3HCC1	G5EA03	G5EA03	394
R3HCC1	ENOX2	Q16206	389
R3HCC1	PGM2	Q96G03	380
R3HCC1	MCTS2	A0A3B3IRV3	377
R3HCC1	HDHD5	Q9BXW7	375

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PPP2R2B	DDX3X	psi-mi:“MI:0914”(association)	0.460
Rcc1	WDR46	psi-mi:“MI:0914”(association)	0.350
SAMD1		psi-mi:“MI:0914”(association)	0.350
NUMA1	SHANK3	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): R3HCC1 (Affinity Capture-RNA), R3HCC1 (Affinity Capture-MS), R3HCC1 (Affinity Capture-MS), R3HCC1 (Affinity Capture-RNA), R3HCC1 (Affinity Capture-MS), R3HCC1 (Proximity Label-MS), R3HCC1 (Affinity Capture-RNA), R3HCC1 (Proximity Label-MS), R3HCC1 (Proximity Label-MS), R3HCC1 (Proximity Label-MS), R3HCC1 (Proximity Label-MS), R3HCC1 (Proximity Label-MS), R3HCC1 (Proximity Label-MS), R3HCC1 (Proximity Label-MS), R3HCC1 (Proximity Label-MS)

ESM2 similar proteins: A0A0J9YX94, A0A0J9YXQ4, A0A0J9YY54, A0A494C1R9, A1L443, A5D7L8, A6NDY0, A6NKD2, E9PGG2, F6SZT2, O19110, O75807, O88852, P0CV98, P0CV99, P0CW00, P0CW01, P0CW24, P0DV79, P17564, P59644, P78358, Q01534, Q0P5N2, Q15735, Q2KI51, Q587J8, Q5R5G8, Q5R6R8, Q5RFC2, Q5SV97, Q60465, Q6P752, Q86V59, Q8BSI6, Q8N9W4, Q8NAG6, Q8NEE8, Q8VD63, Q95LS7

Diamond homologs: Q7Z5L2, Q8BJM3, Q8BSI6, Q9Y3T6

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	50
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1648 predictions. Top by Δscore:

Variant	Effect	Δscore
8:23288154:CGCGG:C	donor_loss	1.0000
8:23288155:GCG:G	donor_gain	1.0000
8:23288157:GGT:G	donor_loss	1.0000
8:23288158:GTGA:G	donor_loss	1.0000
8:23288500:TTACA:T	acceptor_loss	1.0000
8:23288501:TACA:T	acceptor_loss	1.0000
8:23288503:CA:C	acceptor_loss	1.0000
8:23288504:A:AG	acceptor_gain	1.0000
8:23288504:AG:A	acceptor_gain	1.0000
8:23288505:G:GA	acceptor_gain	1.0000
8:23288505:GG:G	acceptor_gain	1.0000
8:23288505:GGC:G	acceptor_gain	1.0000
8:23288505:GGCT:G	acceptor_gain	1.0000
8:23288505:GGCTC:G	acceptor_gain	1.0000
8:23288593:G:GT	donor_gain	1.0000
8:23288632:AA:A	donor_gain	1.0000
8:23288633:AGTA:A	donor_loss	1.0000
8:23288634:G:C	donor_loss	1.0000
8:23288634:G:GG	donor_gain	1.0000
8:23288635:T:A	donor_loss	1.0000
8:23289014:AG:A	acceptor_gain	1.0000
8:23289015:GG:G	acceptor_gain	1.0000
8:23289149:ATCAG:A	donor_loss	1.0000
8:23289152:AGGT:A	donor_loss	1.0000
8:23289153:GGTG:G	donor_loss	1.0000
8:23289154:G:GC	donor_loss	1.0000
8:23289155:T:A	donor_loss	1.0000
8:23290453:G:GG	donor_gain	1.0000
8:23290467:G:GT	donor_gain	1.0000
8:23291359:A:AG	acceptor_gain	1.0000

AlphaMissense

2828 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:23289095:A:C	S64R	0.998
8:23289097:C:A	S64R	0.998
8:23289097:C:G	S64R	0.998
8:23289132:T:A	V76D	0.998
8:23289057:T:C	L51P	0.997
8:23289062:C:G	H53D	0.996
8:23289105:T:A	V67D	0.996
8:23289124:G:C	R73S	0.996
8:23289124:G:T	R73S	0.996
8:23293343:G:C	A356P	0.996
8:23289098:T:C	F65L	0.995
8:23289100:C:A	F65L	0.995
8:23289100:C:G	F65L	0.995
8:23293325:T:A	W350R	0.995
8:23293325:T:C	W350R	0.995
8:23293344:C:A	A356E	0.995
8:23294811:G:C	R380P	0.995
8:23289123:G:C	R73T	0.994
8:23289123:G:T	R73M	0.994
8:23293327:G:C	W350C	0.994
8:23293327:G:T	W350C	0.994
8:23291509:T:C	L334P	0.993
8:23288600:T:C	L26P	0.992
8:23289021:T:C	L39P	0.992
8:23289099:T:C	F65S	0.992
8:23293347:T:C	L357P	0.992
8:23289027:T:C	F41S	0.991
8:23289053:T:G	Y50D	0.991
8:23289090:T:C	L62S	0.991
8:23289129:C:A	T75K	0.991

dbSNP variants (sampled 300 via entrez): RS1000085910 (8:23296301 A>AG), RS1000172227 (8:23292027 G>T), RS1000281192 (8:23287301 C>A,G,T), RS1000323422 (8:23286563 T>C), RS1000330262 (8:23295876 G>A,C), RS1000651847 (8:23287767 G>C), RS1000749122 (8:23292801 C>T), RS1000951660 (8:23293065 C>G,T), RS1001045126 (8:23288077 C>T), RS1001223297 (8:23296327 C>T), RS1001273483 (8:23288115 C>G,T), RS1001284916 (8:23287895 A>C), RS1001495264 (8:23287234 G>A), RS1001584559 (8:23296675 C>A,G), RS1001700683 (8:23296385 T>A)

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

5 associations (top):

Study	Trait	p-value
GCST005957_7	Waist-to-hip ratio adjusted for BMI (age <50)	3.000000e-06
GCST005958_10	Waist-to-hip ratio adjusted for BMI (age >50)	3.000000e-08
GCST005962_21	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-11
GCST011426_28	Systemic lupus erythematosus	9.000000e-06
GCST90093090_7	DHEAS levels	1.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007001	dehydroepiandrosterone sulphate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	2
pirinixic acid	affects binding, decreases expression, increases activity	1
beta-lapachone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Benzo(a)pyrene	affects methylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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