RWDD1

Summary

RWDD1 (RWD domain containing 1, HGNC:20993) is a protein-coding gene on chromosome 6q22.1, encoding RWD domain-containing protein 1 (Q9H446). Protects DRG2 from proteolytic degradation.

Predicted to be involved in cytoplasmic translation and positive regulation of androgen receptor activity. Predicted to be located in cytosol.

Source: NCBI Gene 51389 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total — 1 pathogenic
• MANE Select transcript: NM_015952

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20993
Approved symbol	RWDD1
Name	RWD domain containing 1
Location	6q22.1
Locus type	gene with protein product
Status	Approved
Aliases	DFRP2, PTD013
Ensembl gene	ENSG00000111832
Ensembl biotype	protein_coding
OMIM	620844
Entrez	51389

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000368590, ENST00000466444, ENST00000468204, ENST00000487832, ENST00000517800, ENST00000518117

RefSeq mRNA: 3 — MANE Select: NM_015952 NM_001007464, NM_015952, NM_016104

CCDS: CCDS34520, CCDS43496

Canonical transcript exons

ENST00000466444 — 7 exons

Exon	Start	End
ENSE00002115722	116590888	116590950
ENSE00002117591	116590272	116590404
ENSE00002127796	116592980	116597675
ENSE00002132190	116571504	116571655
ENSE00003509512	116580295	116580360
ENSE00003511380	116588842	116588985
ENSE00003618273	116584727	116584857

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 73.7336 / max 465.3557, expressed in 1822 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69434	55.5394	1813
69431	13.3112	1790
69433	3.4258	1602
69432	1.0203	771
69435	0.4369	205

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.03	gold quality
tendon	UBERON:0000043	97.87	gold quality
body of tongue	UBERON:0011876	97.61	gold quality
body of pancreas	UBERON:0001150	97.44	gold quality
gluteal muscle	UBERON:0002000	97.39	gold quality
saphenous vein	UBERON:0007318	97.34	gold quality
tongue	UBERON:0001723	97.33	gold quality
tongue squamous epithelium	UBERON:0006919	97.20	gold quality
biceps brachii	UBERON:0001507	97.16	gold quality
triceps brachii	UBERON:0001509	97.13	gold quality
cervix squamous epithelium	UBERON:0006922	97.12	gold quality
gingival epithelium	UBERON:0001949	97.11	gold quality
cranial nerve II	UBERON:0000941	97.06	gold quality
heart right ventricle	UBERON:0002080	97.02	gold quality
tendon of biceps brachii	UBERON:0008188	97.01	gold quality
synovial joint	UBERON:0002217	96.98	gold quality
vena cava	UBERON:0004087	96.98	gold quality
superior surface of tongue	UBERON:0007371	96.91	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.86	gold quality
urethra	UBERON:0000057	96.85	gold quality
parietal pleura	UBERON:0002400	96.80	gold quality
tibial artery	UBERON:0007610	96.58	gold quality
popliteal artery	UBERON:0002250	96.57	gold quality
pericardium	UBERON:0002407	96.56	gold quality
medial globus pallidus	UBERON:0002477	96.50	gold quality
pleura	UBERON:0000977	96.46	gold quality
gastrocnemius	UBERON:0001388	96.45	gold quality
gingiva	UBERON:0001828	96.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.37	gold quality
germinal epithelium of ovary	UBERON:0001304	96.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-6	no	323.30
E-CURD-95	no	300.99
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting RWDD1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-648	98.64	66.13	553
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-1271-3P	97.56	64.85	865
HSA-MIR-550A-3-5P	97.56	65.35	823
HSA-MIR-550A-5P	97.56	65.35	823
HSA-MIR-3974	96.56	66.22	928
HSA-MIR-342-3P	96.44	67.48	1344

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rwdd1	ENSDARG00000015930
mus_musculus	Rwdd1	ENSMUSG00000019782
rattus_norvegicus	Rwdd1	ENSRNOG00000042916
drosophila_melanogaster	CG5515	FBGN0039163
caenorhabditis_elegans	T26E3.4	WBGENE00012037

Protein

Protein identifiers

RWD domain-containing protein 1 — Q9H446 (reviewed: Q9H446)

Alternative names: DRG family-regulatory protein 2

All UniProt accessions (4): Q9H446, E5RGQ3, E5RGS5, E5RJE3

UniProt curated annotations — full annotation on UniProt →

Function. Protects DRG2 from proteolytic degradation. May function as a coactivator of the AR/androgen receptor transcription factor during development.

Subunit / interactions. Interacts with DRG2. Interacts with AR/androgen receptor (via NR LBD domain); the interaction is direct and may stimulate AR activity.

Subcellular location. Cytoplasm. Cytosol.

Similarity. Belongs to the RWDD1/GIR2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H446-1	1	yes
Q9H446-2	2

RefSeq proteins (3): NP_001007465, NP_057036, NP_057188 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006575	RWD_dom	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR032378	ZC3H15/TMA46_C	Domain
IPR040213	GIR2-like	Family

Pfam: PF05773, PF16543

UniProt features (21 total): strand 5, helix 4, sequence conflict 2, region of interest 2, modified residue 2, initiator methionine 1, chain 1, turn 1, domain 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2EBM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H446-F1	81.94	0.44

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 (2): 2, 144

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9629569	Protein hydroxylation
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 166 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_TRANSLATION, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_RESPONSE_TO_STEROID_HORMONE, GOBP_RESPONSE_TO_HORMONE, GOBP_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_STEROID_HORMONE_STIMULUS, GOBP_INTRACELLULAR_RECEPTOR_SIGNALING_PATHWAY, GOBP_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, HAND1E47_01, GOBP_ANDROGEN_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (4): cytoplasmic translation (GO:0002181), androgen receptor signaling pathway (GO:0030521), cellular response to oxidative stress (GO:0034599), cellular response to testosterone stimulus (GO:0071394)

GO Molecular Function (2): transcription coactivator activity (GO:0003713), protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
translation	1
nuclear receptor-mediated steroid hormone signaling pathway	1
response to oxidative stress	1
cellular response to chemical stress	1
response to testosterone	1
cellular response to lipid	1
cellular response to ketone	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
binding	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

952 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RWDD1	DRG2	P55039	926
RWDD1	ZC3H15	Q8WU90	854
RWDD1	DRG1	Q9Y295	715
RWDD1	RWDD2A	Q9UIY3	666
RWDD1	RWDD4	Q6NW29	556
RWDD1	ZNF428	Q96B54	518
RWDD1	RABGGTB	P53611	503
RWDD1	DNPH1	O43598	497
RWDD1	RNF24	Q9Y225	492
RWDD1	GCN1	Q92616	490
RWDD1	CCDC97	Q96F63	487
RWDD1	UBL7	Q96S82	462
RWDD1	RWDD2B	P57060	449
RWDD1	GAGE10	A6NGK3	447
RWDD1	MINDY3	Q9H8M7	444

IntAct

26 interactions, top by confidence:

A	B	Type	Score
RWDD1	DRG2	psi-mi:“MI:0915”(physical association)	0.900
DRG2	RWDD1	psi-mi:“MI:0915”(physical association)	0.900
DRG1	RWDD1	psi-mi:“MI:0915”(physical association)	0.800
RWDD1	DRG1	psi-mi:“MI:0915”(physical association)	0.800
DRG2	HSPA8	psi-mi:“MI:0914”(association)	0.530
	RWDD1	psi-mi:“MI:0407”(direct interaction)	0.410
RWDD1	NUDT18	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
CD74		psi-mi:“MI:0914”(association)	0.350
MAP3K14	IKBKG	psi-mi:“MI:0914”(association)	0.350
P2RY6	RAVER1	psi-mi:“MI:0914”(association)	0.350
DRG2	MAPK13	psi-mi:“MI:0914”(association)	0.350
DRG2	DHPS	psi-mi:“MI:0914”(association)	0.350
DRG1	RWDD1	psi-mi:“MI:0915”(physical association)	0.000
DRG2	RWDD1	psi-mi:“MI:0915”(physical association)	0.000
RWDD1	RAC3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): RWDD1 (Two-hybrid), RWDD1 (Two-hybrid), RWDD1 (Affinity Capture-MS), RWDD1 (Two-hybrid), NUDT18 (Two-hybrid), RWDD1 (Two-hybrid), DRG1 (Co-fractionation), RWDD1 (Affinity Capture-Western), RWDD1 (Co-fractionation), RWDD1 (Affinity Capture-MS), RWDD1 (Affinity Capture-MS), RWDD1 (Affinity Capture-MS), RWDD1 (Affinity Capture-MS), RWDD1 (Affinity Capture-MS), RWDD1 (Affinity Capture-MS)

ESM2 similar proteins: A0M8S0, A0M8T1, A3KN28, A4D7R9, Q00PJ0, Q05B58, Q07DV5, Q07DW9, Q07DX8, Q07DY8, Q07E08, Q07E45, Q09YH4, Q09YI5, Q09YJ7, Q09YK8, Q09YN2, Q0VCL3, Q108U3, Q2IBA8, Q2IBE0, Q2IBE8, Q2QL86, Q2QLA6, Q2QLB7, Q2QLD7, Q2QLE8, Q2QLG2, Q32PC9, Q4A1L5, Q4R930, Q4V8C5, Q504Q3, Q5R9K8, Q5ZKS6, Q68FW3, Q6AZ50, Q6DDX7, Q6IE70, Q8K4P7

Diamond homologs: O94721, Q99ND9, Q9CQK7, Q9H446, P15442

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
180224	NC_000006.11:g.(112511751_112511752)_(118037595_118037596)del	Pathogenic

SpliceAI

1265 predictions. Top by Δscore:

Variant	Effect	Δscore
6:116580291:GCAGT:G	acceptor_loss	1.0000
6:116580292:CA:C	acceptor_loss	1.0000
6:116580293:A:AG	acceptor_gain	1.0000
6:116580293:AGT:A	acceptor_loss	1.0000
6:116580294:G:GA	acceptor_gain	1.0000
6:116580294:GT:G	acceptor_gain	1.0000
6:116580294:GTA:G	acceptor_gain	1.0000
6:116580294:GTAT:G	acceptor_gain	1.0000
6:116580294:GTATT:G	acceptor_gain	1.0000
6:116580356:TGAAA:T	donor_gain	1.0000
6:116580357:GAAA:G	donor_gain	1.0000
6:116580357:GAAAG:G	donor_gain	1.0000
6:116580358:A:T	donor_gain	1.0000
6:116580358:AAA:A	donor_gain	1.0000
6:116580358:AAAGT:A	donor_loss	1.0000
6:116580359:AA:A	donor_gain	1.0000
6:116580359:AAGT:A	donor_loss	1.0000
6:116580360:AG:A	donor_loss	1.0000
6:116580361:G:GG	donor_gain	1.0000
6:116580361:GT:G	donor_loss	1.0000
6:116580362:TAA:T	donor_loss	1.0000
6:116588830:T:TA	acceptor_gain	1.0000
6:116588832:T:TA	acceptor_gain	1.0000
6:116588837:CACA:C	acceptor_loss	1.0000
6:116588838:A:AG	acceptor_gain	1.0000
6:116588838:ACAG:A	acceptor_gain	1.0000
6:116588839:C:G	acceptor_gain	1.0000
6:116588840:A:AG	acceptor_gain	1.0000
6:116588840:AG:A	acceptor_gain	1.0000
6:116588840:AGGCT:A	acceptor_gain	1.0000

AlphaMissense

1634 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:116588872:T:C	F101L	1.000
6:116588874:T:A	F101L	1.000
6:116588874:T:G	F101L	1.000
6:116590294:T:A	V146D	1.000
6:116590308:T:C	F151L	1.000
6:116590309:T:C	F151S	1.000
6:116590310:C:A	F151L	1.000
6:116590310:C:G	F151L	1.000
6:116590319:G:C	W154C	1.000
6:116590319:G:T	W154C	1.000
6:116590329:T:C	F158L	1.000
6:116590331:T:A	F158L	1.000
6:116590331:T:G	F158L	1.000
6:116590888:G:A	G183E	1.000
6:116590897:T:C	L186P	1.000
6:116590899:T:C	F187L	1.000
6:116590900:T:G	F187C	1.000
6:116590901:T:A	F187L	1.000
6:116590901:T:G	F187L	1.000
6:116593012:T:C	F215L	1.000
6:116593014:C:A	F215L	1.000
6:116593014:C:G	F215L	1.000
6:116571613:G:A	E11K	0.999
6:116571614:A:T	E11V	0.999
6:116571615:G:C	E11D	0.999
6:116571615:G:T	E11D	0.999
6:116571622:G:C	A14P	0.999
6:116571623:C:A	A14D	0.999
6:116571626:T:C	L15P	0.999
6:116571631:T:C	S17P	0.999

dbSNP variants (sampled 300 via entrez): RS1000231788 (6:116584729 G>A), RS1000243613 (6:116572456 T>C), RS1000858764 (6:116586310 T>A), RS1000910632 (6:116578438 A>G), RS1001177463 (6:116578305 T>C), RS1001363926 (6:116585786 C>G), RS1001625471 (6:116586049 G>A,T), RS1001755325 (6:116578140 C>T), RS1002018428 (6:116573162 T>C), RS1002070141 (6:116572208 T>C), RS1002350188 (6:116583748 C>T), RS1002458686 (6:116591785 G>C), RS1002582307 (6:116591460 A>C), RS1002669856 (6:116571147 G>A,C), RS1002719611 (6:116585481 G>C)

Disease associations

OMIM: gene MIM:620844 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Arsenic	increases expression, affects methylation, increases abundance	2
Valproic Acid	affects cotreatment, increases expression, affects expression	2
GSK-J4	increases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
AM 251	increases expression	1
K 7174	decreases expression	1
bisphenol B	increases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Cytarabine	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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