WDR83OS

Summary

WDR83OS (WD repeat domain 83 opposite strand, HGNC:30203) is a protein-coding gene on chromosome 19p13.13, encoding PAT complex subunit Asterix (Q9Y284). Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes.

Enables protein folding chaperone. Involved in multi-pass transmembrane protein insertion into ER membrane. Located in endoplasmic reticulum membrane. Part of multi-pass translocon complex and protein folding chaperone complex.

Source: NCBI Gene 51398 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with variable familial hypercholanemia (Strong, GenCC)
• Clinical variants (ClinVar): 3 total — 1 pathogenic
• Phenotypes (HPO): 107
• MANE Select transcript: NM_016145

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30203
Approved symbol	WDR83OS
Name	WD repeat domain 83 opposite strand
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	PTD008, PAT10
Ensembl gene	ENSG00000105583
Ensembl biotype	protein_coding
OMIM	618474
Entrez	51398

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000222190, ENST00000596731, ENST00000598732, ENST00000862750

RefSeq mRNA: 1 — MANE Select: NM_016145 NM_016145

CCDS: CCDS12274

Canonical transcript exons

ENST00000596731 — 4 exons

Exon	Start	End
ENSE00000681977	12668520	12668617
ENSE00003168836	12668073	12668425
ENSE00003489102	12669128	12669233
ENSE00003831905	12669354	12669415

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 151.5166 / max 551.6082, expressed in 1827 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179325	151.5166	1827

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	98.95	gold quality
pituitary gland	UBERON:0000007	98.92	gold quality
fallopian tube	UBERON:0003889	98.90	gold quality
left adrenal gland	UBERON:0001234	98.87	gold quality
right adrenal gland cortex	UBERON:0035827	98.87	gold quality
left adrenal gland cortex	UBERON:0035825	98.86	gold quality
endocervix	UBERON:0000458	98.85	gold quality
left ovary	UBERON:0002119	98.85	gold quality
adenohypophysis	UBERON:0002196	98.85	gold quality
body of pancreas	UBERON:0001150	98.81	gold quality
smooth muscle tissue	UBERON:0001135	98.80	gold quality
right ovary	UBERON:0002118	98.77	gold quality
skin of leg	UBERON:0001511	98.71	gold quality
left lobe of thyroid gland	UBERON:0001120	98.70	gold quality
fundus of stomach	UBERON:0001160	98.69	gold quality
right coronary artery	UBERON:0001625	98.68	gold quality
gall bladder	UBERON:0002110	98.68	gold quality
skin of abdomen	UBERON:0001416	98.67	gold quality
zone of skin	UBERON:0000014	98.66	gold quality
right lobe of thyroid gland	UBERON:0001119	98.66	gold quality
ectocervix	UBERON:0012249	98.65	gold quality
stromal cell of endometrium	CL:0002255	98.63	gold quality
metanephros cortex	UBERON:0010533	98.63	gold quality
body of stomach	UBERON:0001161	98.61	gold quality
left coronary artery	UBERON:0001626	98.61	gold quality
islet of Langerhans	UBERON:0000006	98.60	gold quality
prostate gland	UBERON:0002367	98.59	gold quality
granulocyte	CL:0000094	98.58	gold quality
pancreas	UBERON:0001264	98.58	gold quality
body of uterus	UBERON:0009853	98.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.47
E-CURD-10	no	336.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting WDR83OS, 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-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-12128	96.67	66.98	1471
HSA-MIR-7973	96.48	65.54	502
HSA-MIR-642B-5P	96.37	67.26	745
HSA-MIR-5195-5P	90.84	65.09	287

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wdr83os	ENSDARG00000025554
mus_musculus	Wdr83os	ENSMUSG00000059355
rattus_norvegicus	Wdr83os	ENSRNOG00000033611
drosophila_melanogaster	CG10674	FBGN0035592
caenorhabditis_elegans		WBGENE00019607

Protein

Protein identifiers

PAT complex subunit Asterix — Q9Y284 (reviewed: Q9Y284)

Alternative names: Protein associated with the ER translocon of 10kDa, WD repeat domain 83 opposite strand, WDR83 opposite strand

All UniProt accessions (3): Q9Y284, A0A0A0MQS5, M0R1D5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes. The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions. Within the MPT complex, the PAT subcomplex sequesters any highly polar regions in the transmembrane domains away from the non-polar membrane environment until they can be buried in the interior of the fully assembled protein. Within the PAT subcomplex, WDR83OS/Asterix binds to and redirects the substrate to a location behind the SEC61 complex.

Subunit / interactions. Component of the PAT complex, composed of WDR83OS/Asterix and CCDC47. The PAT complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47). The MPT complex associates with the SEC61 complex.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Neurodevelopmental disorder with variable familial hypercholanemia (NEDFHCA) [MIM:621016] An autosomal recessive disorder characterized by global developmental delay, motor and speech delay, impaired intellectual development, intractable itching, and signs of liver dysfunction including increased serum bile acids, hepatomegaly, elevated liver enzymes, and gallstones. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Asterix family.

RefSeq proteins (1): NP_057229* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005351	ASTER	Family

Pfam: PF03669

UniProt features (14 total): topological domain 4, sequence variant 3, transmembrane region 3, initiator methionine 1, chain 1, modified residue 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y284-F1	62.09	0.00

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): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 389 (showing top): MODULE_151, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, CAGCTG_AP4_Q5, GOBP_PROTEIN_MATURATION, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_PROTEIN_FOLDING, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_ORGANIZATION, HU_GENOTOXIC_DAMAGE_24HR, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_PROTEIN_INSERTION_INTO_MEMBRANE

GO Biological Process (3): protein insertion into ER membrane (GO:0045048), multi-pass transmembrane protein insertion into ER membrane (GO:0160063), protein folding (GO:0006457)

GO Molecular Function (2): protein folding chaperone (GO:0044183), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), protein folding chaperone complex (GO:0101031), multi-pass translocon complex (GO:0160064), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endoplasmic reticulum organization	1
protein localization to organelle	1
protein insertion into membrane	1
protein insertion into ER membrane	1
cellular process	1
protein maturation	1
molecular_function	1
protein folding	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular protein-containing complex	1
ER membrane insertion complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR83OS	TUBB2B	Q9BVA1	894
WDR83OS	TUBB4B	P05217	765
WDR83OS	TUBB2A	Q13885	750
WDR83OS	TMEM208	Q9BTX3	650
WDR83OS	WDR83	Q9BRX9	646
WDR83OS	TNPO2	O14787	514
WDR83OS	NUDT22	Q9BRQ3	499
WDR83OS	CCDC47	Q96A33	486
WDR83OS	PIWIL4	Q7Z3Z4	486
WDR83OS	PIWIL1	Q96J94	485
WDR83OS	GTF3A	Q92664	474
WDR83OS	HELT	A6NFD8	473
WDR83OS	ATP13A2	Q9NQ11	469
WDR83OS	ABCB11	O95342	448
WDR83OS	PSPN	O60542	439

IntAct

9 interactions, top by confidence:

A	B	Type	Score
ZNF534	WDR83OS	psi-mi:“MI:0915”(physical association)	0.560
CCDC47	WDR83OS	psi-mi:“MI:0915”(physical association)	0.560
WDR83OS	ATP13A2	psi-mi:“MI:0915”(physical association)	0.370
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350
ZNF534	WDR83OS	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): WDR83OS (Affinity Capture-RNA), TRPC6 (Affinity Capture-Western), TMEM208 (Affinity Capture-Western), TMEM208 (Co-localization), TRPC6 (Co-localization), WDR83OS (Positive Genetic), ZNF534 (Two-hybrid), WDR83OS (Affinity Capture-MS), WDR83OS (Negative Genetic), WDR83OS (Affinity Capture-MS), WDR83OS (Affinity Capture-MS), WDR83OS (Affinity Capture-MS), WDR83OS (Affinity Capture-RNA), WDR83OS (Two-hybrid)

ESM2 similar proteins: A0A7H0DNA7, A0A8I3NQW8, B2RWJ3, C4QVD6, C5DQY5, C7Z504, D1ZRK4, E9EM69, F1LXS7, F5HDD0, F8RT80, O36388, O48670, O94592, P0C655, P20987, P33835, P36707, Q04684, Q09366, Q09714, Q09952, Q09993, Q197D8, Q1KZ54, Q1L864, Q21642, Q28IL7, Q2H3I7, Q2M2T6, Q54U35, Q5M7C7, Q5M9B7, Q5XJX0, Q64919, Q6GNY6, Q6NVQ1, Q6Q7K0, Q6QA74, Q6ZWX0

Diamond homologs: A0A8I3NQW8, F8RT80, Q09993, Q2M2T6, Q6Q7K0, Q6ZWX0, Q9U516, Q9VRJ8, Q9Y284

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WDR83OS	“form complex”	“PAT intramembrane chaperone complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1457169	NC_000019.9:g.(?12757434)(13617038_?)del	Pathogenic

SpliceAI

603 predictions. Top by Δscore:

Variant	Effect	Δscore
19:12668518:A:AC	donor_gain	1.0000
19:12668519:C:CC	donor_gain	1.0000
19:12668532:A:AC	donor_gain	1.0000
19:12668532:AT:A	donor_gain	1.0000
19:12668618:C:CC	acceptor_gain	1.0000
19:12669146:CATG:C	donor_gain	1.0000
19:12669350:TCA:T	donor_loss	1.0000
19:12669351:CAC:C	donor_loss	1.0000
19:12669352:A:AT	donor_loss	1.0000
19:12668506:A:AG	acceptor_gain	0.9900
19:12668506:AG:A	acceptor_gain	0.9900
19:12668507:G:GG	acceptor_gain	0.9900
19:12668507:GG:G	acceptor_gain	0.9900
19:12668533:T:C	donor_gain	0.9900
19:12668542:T:TA	donor_gain	0.9900
19:12668613:TTCAG:T	acceptor_gain	0.9900
19:12668614:TCAG:T	acceptor_gain	0.9900
19:12668615:CAG:C	acceptor_gain	0.9900
19:12668615:CAGC:C	acceptor_gain	0.9900
19:12668616:AG:A	acceptor_gain	0.9900
19:12668616:AGC:A	acceptor_loss	0.9900
19:12668618:C:A	acceptor_loss	0.9900
19:12668618:CT:C	acceptor_loss	0.9900
19:12669124:CCACC:C	donor_loss	0.9900
19:12669126:A:AT	donor_loss	0.9900
19:12669127:CC:C	donor_loss	0.9900
19:12669127:CCTTA:C	donor_loss	0.9900
19:12669235:T:A	acceptor_loss	0.9900
19:12669350:TCAC:T	donor_loss	0.9900
19:12669352:A:AC	donor_gain	0.9900

AlphaMissense

716 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12668393:A:G	L96P	1.000
19:12668411:G:T	A90D	1.000
19:12668412:C:G	A90P	1.000
19:12668423:A:G	L86P	1.000
19:12668423:A:T	L86Q	1.000
19:12668525:G:C	S83R	1.000
19:12668525:G:T	S83R	1.000
19:12668527:T:G	S83R	1.000
19:12668528:A:C	S82R	1.000
19:12668528:A:T	S82R	1.000
19:12668530:T:G	S82R	1.000
19:12668540:C:A	K78N	1.000
19:12668540:C:G	K78N	1.000
19:12668548:C:G	D76H	1.000
19:12668568:G:T	A69D	1.000
19:12668569:C:G	A69P	1.000
19:12668573:G:C	S67R	1.000
19:12668573:G:T	S67R	1.000
19:12668575:T:G	S67R	1.000
19:12668586:C:T	C63Y	1.000
19:12668587:A:G	C63R	1.000
19:12668595:G:T	A60D	1.000
19:12668600:C:A	W58C	1.000
19:12668600:C:G	W58C	1.000
19:12668602:A:G	W58R	1.000
19:12668602:A:T	W58R	1.000
19:12668604:G:T	A57D	1.000
19:12668608:A:G	C56R	1.000
19:12668612:C:A	K54N	1.000
19:12668612:C:G	K54N	1.000

dbSNP variants (sampled 300 via entrez): RS1000546631 (19:12669427 C>G,T), RS1000917887 (19:12669249 G>A,C), RS1002339 (19:12669973 C>A,T), RS1002678776 (19:12668191 C>T), RS1003915148 (19:12668126 C>G,T), RS1004519211 (19:12667801 G>C), RS1005332547 (19:12670820 G>A,T), RS1007362557 (19:12670460 C>G,T), RS1007831581 (19:12669628 T>C), RS1008134656 (19:12669435 G>A), RS1008869020 (19:12668149 C>A,T), RS1009357198 (19:12669128 C>G,T), RS1009624331 (19:12668953 C>T), RS1011264881 (19:12670403 A>C), RS1012591593 (19:12671041 A>C)

Disease associations

OMIM: gene MIM:618474 | disease phenotypes: MIM:108500, MIM:231670, MIM:610333, MIM:617106

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with variable familial hypercholanemia	Strong	Autosomal recessive

Mondo (5): episodic ataxia type 2 (MONDO:0007163), glutaryl-CoA dehydrogenase deficiency (MONDO:0009281), Aicardi-Goutieres syndrome 4 (MONDO:0012472), developmental and epileptic encephalopathy, 42 (MONDO:0014917), neurodevelopmental disorder with variable familial hypercholanemia (MONDO:0975877)

Orphanet (3): Glutaryl-CoA dehydrogenase deficiency (Orphanet:25), Aicardi-Goutières syndrome (Orphanet:51), Familial paroxysmal ataxia (Orphanet:97)

HPO phenotypes

107 total (30 of 107 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000122	Unilateral renal agenesis
HP:0000154	Wide mouth
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000384	Preauricular skin tag
HP:0000414	Bulbous nose
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000527	Long eyelashes
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure
HP:0000601	Hypotelorism
HP:0000664	Synophrys
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C563681	Aicardi-Goutieres Syndrome 4 (supp.)
C535506	Episodic Ataxia, Type 2 (supp.)
C536833	Glutaric Acidemia I (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, increases expression	1
K 7174	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Doxorubicin	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3LC	Abcam HEK293T WDR83OS KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07221292	PHASE3	NOT_YET_RECRUITING	Pivotal Study of N-acetyl-L-leucine for CACNA1A
NCT01543750	PHASE2	WITHDRAWN	4-Aminopyridine in Episodic Ataxia Type 2
NCT06217861	PHASE1	RECRUITING	A Study to Evaluate the Tolerability, Safety and Efficacy of VGM-R02b
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan