RWDD2A

Summary

RWDD2A (RWD domain containing 2A, HGNC:21385) is a protein-coding gene on chromosome 6q14.1, encoding RWD domain-containing protein 2A (Q9UIY3).

At a glance

• Clinical variants (ClinVar): 34 total — 1 pathogenic
• MANE Select transcript: NM_033411

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21385
Approved symbol	RWDD2A
Name	RWD domain containing 2A
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC13523, dJ747H23.2
Ensembl gene	ENSG00000013392
Ensembl biotype	protein_coding
Entrez	112611

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000369724, ENST00000875848, ENST00000925504, ENST00000925505

RefSeq mRNA: 5 — MANE Select: NM_033411 NM_001322335, NM_001322336, NM_001322337, NM_001322339, NM_033411

CCDS: CCDS4998

Canonical transcript exons

ENST00000369724 — 3 exons

Exon	Start	End
ENSE00000468718	83194312	83194652
ENSE00001737924	83195595	83198935
ENSE00001937663	83193357	83193443

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 86.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0416 / max 97.5973, expressed in 1701 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68773	7.8979	1696
68772	0.1437	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	86.65	gold quality
sperm	CL:0000019	84.78	gold quality
male germ cell	CL:0000015	82.78	gold quality
body of pancreas	UBERON:0001150	81.54	gold quality
middle temporal gyrus	UBERON:0002771	81.04	gold quality
cortical plate	UBERON:0005343	80.03	gold quality
pancreas	UBERON:0001264	78.89	gold quality
left adrenal gland	UBERON:0001234	78.86	gold quality
right adrenal gland	UBERON:0001233	78.74	gold quality
left adrenal gland cortex	UBERON:0035825	78.74	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.62	gold quality
islet of Langerhans	UBERON:0000006	78.46	gold quality
prefrontal cortex	UBERON:0000451	78.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.80	gold quality
right adrenal gland cortex	UBERON:0035827	77.53	gold quality
right frontal lobe	UBERON:0002810	77.50	gold quality
adrenal cortex	UBERON:0001235	77.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.02	gold quality
stromal cell of endometrium	CL:0002255	77.02	gold quality
Brodmann (1909) area 23	UBERON:0013554	77.01	gold quality
adrenal gland	UBERON:0002369	76.95	gold quality
prostate gland	UBERON:0002367	76.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.56	gold quality
cerebellar hemisphere	UBERON:0002245	76.54	gold quality
cerebellar cortex	UBERON:0002129	76.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.02	gold quality
primary visual cortex	UBERON:0002436	75.75	gold quality
neocortex	UBERON:0001950	75.74	gold quality
frontal cortex	UBERON:0001870	75.71	gold quality
right lobe of liver	UBERON:0001114	75.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

130 targeting RWDD2A, 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-340-5P	100.00	72.50	4437
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rwdd2a	ENSMUSG00000032417
rattus_norvegicus	Rwdd2a	ENSRNOG00000009599
drosophila_melanogaster	CG30338	FBGN0050338

Paralogs (1): RWDD2B (ENSG00000156253)

Protein

Protein identifiers

RWD domain-containing protein 2A — Q9UIY3 (reviewed: Q9UIY3)

All UniProt accessions (1): Q9UIY3

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UIY3-1	1	yes
Q9UIY3-2	2

RefSeq proteins (5): NP_001309264, NP_001309265, NP_001309266, NP_001309268, NP_219479* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006575	RWD_dom	Domain
IPR010541	Prp3_C	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR017359	Phi-like	Family
IPR059181	RWDD2A-B_C	Domain

Pfam: PF05773, PF06544

UniProt features (16 total): helix 6, strand 5, chain 1, domain 1, splice variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DAW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UIY3-F1	85.57	0.58

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): NKX25_02, HIF1_Q3, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, YYCATTCAWW_UNKNOWN, SCGGAAGY_ELK1_02, chr6q14, DUTERTRE_ESTRADIOL_RESPONSE_24HR_DN, E47_02, GSE14699_NAIVE_VS_ACT_CD8_TCELL_UP, DACH1_TARGET_GENES, GLI1_TARGET_GENES, IRF5_TARGET_GENES, NFKBIA_TARGET_GENES, ZSCAN31_TARGET_GENES, MIR3658

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RWDD2A	RWDD1	Q9H446	666
RWDD2A	C11orf71	Q6IPW1	557
RWDD2A	KIAA1755	Q5JYT7	485
RWDD2A	C6orf163	Q5TEZ5	480
RWDD2A	RWDD4	Q6NW29	478
RWDD2A	ZBTB47	Q9UFB7	476
RWDD2A	MEAK7	Q6P9B6	466
RWDD2A	C22orf39	Q6P5X5	463
RWDD2A	RNF103	O00237	436
RWDD2A	PRDM11	Q9NQV5	429
RWDD2A	SMIM8	Q96KF7	414
RWDD2A	ENTREP1	Q15884	391
RWDD2A	PRPSAP2	O60256	390
RWDD2A	RAI2	Q9Y5P3	390
RWDD2A	UBE3D	Q7Z6J8	386

IntAct

14 interactions, top by confidence:

A	B	Type	Score
RWDD2A	ATG7	psi-mi:“MI:0915”(physical association)	0.640
RWDD2A	ATG7	psi-mi:“MI:0914”(association)	0.640
ARHGEF6	RWDD2A	psi-mi:“MI:0915”(physical association)	0.560
MCMBP	RWDD2A	psi-mi:“MI:0915”(physical association)	0.560
PSMB1	RWDD2A	psi-mi:“MI:0915”(physical association)	0.560
ERBB3	RWDD2A	psi-mi:“MI:0915”(physical association)	0.370
ARHGEF6	RWDD2A	psi-mi:“MI:0915”(physical association)	0.000
MCMBP	RWDD2A	psi-mi:“MI:0915”(physical association)	0.000
PSMB1	RWDD2A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): GABARAP (Affinity Capture-MS), ATG7 (Affinity Capture-MS), ATG7 (Affinity Capture-MS), RWDD2A (Two-hybrid), ARHGEF6 (Two-hybrid), MCMBP (Two-hybrid), RWDD2A (Two-hybrid), ATG7 (Affinity Capture-MS), CASP6 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), RWDD2A (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0JMU5, A1A5P5, A3KN24, A6QLC7, A9ULH0, B2RXC1, B5DF07, B6DMK2, B6NXD5, O60678, O70467, O75417, P0C7N0, Q08B12, Q14AI0, Q19QT9, Q28ES8, Q2KI89, Q32LH3, Q32NV1, Q32PH0, Q3EBC8, Q4R6P2, Q5E9U4, Q5R629, Q5RDC7, Q5XGG3, Q5ZI89, Q5ZJM3, Q641F8, Q68F70, Q6DHJ1, Q6GMB0, Q6GPP1, Q6NU25, Q6PBV4, Q6PD74, Q7Z392, Q8BP74, Q8BSA9

Diamond homologs: P57060, Q4R6P2, Q5R9U9, Q99M03, Q9D9S3, Q9UIY3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	31
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
224831	Single allele	Pathogenic

SpliceAI

641 predictions. Top by Δscore:

Variant	Effect	Δscore
6:83195591:TAAG:T	acceptor_loss	1.0000
6:83195592:AAGGT:A	acceptor_gain	1.0000
6:83195593:A:AG	acceptor_loss	1.0000
6:83195593:A:G	acceptor_gain	1.0000
6:83195594:G:GC	acceptor_loss	1.0000
6:83193442:GG:G	donor_gain	0.9900
6:83193443:GG:G	donor_gain	0.9900
6:83194654:T:G	donor_loss	0.9900
6:83195587:A:AG	acceptor_gain	0.9900
6:83195588:T:G	acceptor_gain	0.9900
6:83195592:A:AG	acceptor_gain	0.9900
6:83195594:G:GG	acceptor_gain	0.9900
6:83195594:GGT:G	acceptor_gain	0.9900
6:83193441:AGGGT:A	donor_loss	0.9800
6:83193444:GTGAG:G	donor_loss	0.9800
6:83193445:T:A	donor_loss	0.9800
6:83194524:A:AG	acceptor_gain	0.9800
6:83194529:A:G	acceptor_gain	0.9800
6:83194653:G:GG	donor_gain	0.9800
6:83195592:AAG:A	acceptor_gain	0.9800
6:83195641:TAG:T	acceptor_gain	0.9700
6:83193444:G:GG	donor_gain	0.9600
6:83193446:GAG:G	donor_loss	0.9600
6:83195642:A:T	acceptor_gain	0.9600
6:83195643:G:T	acceptor_gain	0.9600
6:83193730:G:T	donor_gain	0.9500
6:83194145:TTGA:T	donor_gain	0.9500
6:83195179:GTT:G	acceptor_gain	0.9500
6:83194516:T:G	acceptor_gain	0.9400
6:83194525:A:G	acceptor_gain	0.9400

AlphaMissense

1949 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:83195868:T:A	W159R	0.999
6:83195868:T:C	W159R	0.999
6:83195947:G:A	G185E	0.999
6:83196039:T:A	W216R	0.999
6:83196039:T:C	W216R	0.999
6:83196041:G:C	W216C	0.999
6:83196041:G:T	W216C	0.999
6:83195863:G:C	R157P	0.998
6:83195880:C:G	H163D	0.998
6:83195949:T:C	F186L	0.998
6:83195951:T:A	F186L	0.998
6:83195951:T:G	F186L	0.998
6:83195962:G:A	G190E	0.998
6:83196202:T:C	L270P	0.998
6:83195877:A:C	S162R	0.997
6:83195879:T:A	S162R	0.997
6:83195879:T:G	S162R	0.997
6:83195882:C:A	H163Q	0.997
6:83195882:C:G	H163Q	0.997
6:83195962:G:T	G190V	0.997
6:83195967:C:T	P192S	0.997
6:83195971:G:A	G193D	0.997
6:83195981:T:G	C196W	0.997
6:83196059:G:C	K222N	0.997
6:83196059:G:T	K222N	0.997
6:83195946:G:A	G185R	0.996
6:83195946:G:C	G185R	0.996
6:83195950:T:C	F186S	0.996
6:83195968:C:A	P192H	0.996
6:83195979:T:C	C196R	0.996

dbSNP variants (sampled 300 via entrez): RS1000012132 (6:83192683 T>C), RS1000123695 (6:83198869 G>T), RS1000848297 (6:83197677 T>C), RS1000972192 (6:83193351 C>A,T), RS1001152535 (6:83191738 T>C), RS1001976525 (6:83194890 A>G), RS1002028632 (6:83195164 C>T), RS1002051956 (6:83192791 T>C), RS1002353310 (6:83191624 T>C,G), RS1002800743 (6:83195247 C>T), RS1003932669 (6:83192013 T>A,C,G), RS1004090359 (6:83194183 G>A), RS1004476526 (6:83198161 G>T), RS1004641906 (6:83196703 A>C), RS1004921102 (6:83192536 T>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:216920, MIM:615816

GenCC curated gene-disease

Mondo (1): immunodeficiency 23 (MONDO:0014353)

Orphanet (1): PGM3-CDG (Orphanet:443811)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565684	Combined Inflammatory and Immunologic Defect (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, decreases expression, affects expression	7
trichostatin A	decreases expression, affects cotreatment	3
Cyclosporine	increases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Tunicamycin	increases expression	1
Aflatoxin B1	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01454856	Not specified	TERMINATED	Perioperative Evaluation of Immuno-inflammatory Parameters