WRAP73

Summary

WRAP73 (WD repeat containing, antisense to TP73, HGNC:12759) is a protein-coding gene on chromosome 1p36.32, encoding WD repeat-containing protein WRAP73 (Q9P2S5). The SSX2IP:WRAP73 complex is proposed to act as regulator of spindle anchoring at the mitotic centrosome.

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Studies of the related mouse protein suggest that the encoded protein may play a role in the process of ossification.

Source: NCBI Gene 49856 — RefSeq curated summary.

At a glance

• Gene–disease (curated): anterior segment dysgenesis (Moderate, GenCC)
• Clinical variants (ClinVar): 114 total
• MANE Select transcript: NM_017818

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12759
Approved symbol	WRAP73
Name	WD repeat containing, antisense to TP73
Location	1p36.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000116213
Ensembl biotype	protein_coding
OMIM	606040
Entrez	49856

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 16 protein_coding, 5 retained_intron

ENST00000270708, ENST00000378322, ENST00000419924, ENST00000424367, ENST00000465916, ENST00000469643, ENST00000471223, ENST00000479331, ENST00000494884, ENST00000497940, ENST00000855126, ENST00000855127, ENST00000855128, ENST00000855129, ENST00000855130, ENST00000920579, ENST00000920580, ENST00000920581, ENST00000960492, ENST00000960493, ENST00000960494

RefSeq mRNA: 1 — MANE Select: NM_017818 NM_017818

CCDS: CCDS48

Canonical transcript exons

ENST00000270708 — 12 exons

Exon	Start	End
ENSE00000734299	3646666	3646782
ENSE00000734303	3638750	3638822
ENSE00000734306	3636995	3637098
ENSE00001659258	3633398	3633503
ENSE00001697450	3630770	3631117
ENSE00001748742	3649931	3650103
ENSE00001797222	3631466	3631657
ENSE00003480267	3635944	3636030
ENSE00003492457	3635160	3635294
ENSE00003566716	3647408	3647560
ENSE00003685083	3634997	3635074
ENSE00003789737	3632213	3632338

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 91.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1278 / max 63.7689, expressed in 1779 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9951	7.6761	1762
9950	1.4517	792

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	91.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.65	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.13	gold quality
cerebellar hemisphere	UBERON:0002245	88.52	gold quality
cerebellar cortex	UBERON:0002129	88.38	gold quality
mucosa of transverse colon	UBERON:0004991	87.65	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.59	gold quality
spleen	UBERON:0002106	87.11	gold quality
adenohypophysis	UBERON:0002196	87.02	gold quality
apex of heart	UBERON:0002098	86.98	gold quality
blood	UBERON:0000178	86.80	gold quality
cerebellum	UBERON:0002037	86.77	gold quality
monocyte	CL:0000576	86.68	gold quality
body of stomach	UBERON:0001161	86.66	gold quality
oocyte	CL:0000023	86.39	gold quality
leukocyte	CL:0000738	86.35	gold quality
mononuclear cell	CL:0000842	86.27	gold quality
metanephros cortex	UBERON:0010533	86.17	gold quality
body of pancreas	UBERON:0001150	85.73	gold quality
right adrenal gland	UBERON:0001233	85.70	gold quality
pituitary gland	UBERON:0000007	85.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.58	gold quality
lower esophagus	UBERON:0013473	85.57	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.57	gold quality
transverse colon	UBERON:0001157	85.54	gold quality
stromal cell of endometrium	CL:0002255	85.45	gold quality
small intestine	UBERON:0002108	85.35	gold quality
right ovary	UBERON:0002118	85.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.27	gold quality
right adrenal gland cortex	UBERON:0035827	85.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

17 targeting WRAP73, 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-5692A	100.00	74.40	6850
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-6779-3P	97.51	65.82	789
HSA-MIR-34A-3P	96.80	67.70	805

Literature-anchored findings (GeneRIF, showing 4)

• Knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. (PMID:26545777)
• Cep135 is required for the recruitment of WDR8 to centrioles. (PMID:26675238)
• Exome sequencing and functional studies in zebrafish identify WDR8 as the causative gene for isolated Microspherophakia in Indian families. (PMID:33693649)
• Mitotic Maturation Compensates for Premature Centrosome Splitting and PCM Loss in Human cep135 Knockout Cells. (PMID:35406752)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	wrap73	ENSDARG00000009557
mus_musculus	Wrap73	ENSMUSG00000029029
rattus_norvegicus	Wrap73	ENSRNOG00000014805

Protein

Protein identifiers

WD repeat-containing protein WRAP73 — Q9P2S5 (reviewed: Q9P2S5)

Alternative names: WD repeat-containing protein 8, WD repeat-containing protein antisense to TP73 gene

All UniProt accessions (6): Q9P2S5, A0A0A0MRV3, A0A384MQZ3, J3KTP2, Q5T0D5, Q5TBW1

UniProt curated annotations — full annotation on UniProt →

Function. The SSX2IP:WRAP73 complex is proposed to act as regulator of spindle anchoring at the mitotic centrosome. Required for the centrosomal localization of SSX2IP and normal mitotic bipolar spindle morphology. Required for the targeting of centriole satellite proteins to centrosomes such as of PCM1, SSX2IP, CEP290 and PIBF1/CEP90. Required for ciliogenesis and involved in the removal of the CEP97:CCP110 complex from the mother centriole. Involved in ciliary vesicle formation at the mother centriole and required for the docking of vesicles to the basal body during ciliogenesis; may promote docking of RAB8A- and ARL13B-containing vesicles.

Subunit / interactions. Interacts with SSX2IP.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Centriolar satellite.

Tissue specificity. Ubiquitous. Predominant expression in heart, brain, liver, thymus, prostate, and testis, and barely detectable expression in lung.

RefSeq proteins (1): NP_060288* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR052778	Centrosome-WD_assoc	Family

Pfam: PF00400

UniProt features (12 total): repeat 6, sequence conflict 2, sequence variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2S5-F1	90.26	0.84

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): 281

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 138 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, BENPORATH_ES_WITH_H3K27ME3, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, MUELLER_PLURINET, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_MITOTIC_SPINDLE_ASSEMBLY, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_ORGANELLE_FISSION, MARTINEZ_RB1_TARGETS_DN, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME

GO Biological Process (4): cell projection organization (GO:0030030), mitotic spindle assembly (GO:0090307), positive regulation of non-motile cilium assembly (GO:1902857), microtubule anchoring at mitotic spindle pole body (GO:1990810)

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

GO Cellular Component (8): cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), microtubule organizing center (GO:0005815), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), MWP complex (GO:1990811), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
microtubule organizing center	3
intracellular membraneless organelle	2
cellular component organization	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
mitotic nuclear division	1
positive regulation of cilium assembly	1
regulation of non-motile cilium assembly	1
non-motile cilium assembly	1
microtubule anchoring at spindle pole body	1
mitotic spindle assembly	1
microtubule cytoskeleton organization involved in mitosis	1
binding	1
intracellular anatomical structure	1
centriole	1
microtubule cytoskeleton	1
centrosome	1
cilium	1
protein-containing complex	1

Protein interactions and networks

STRING

940 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WRAP73	MEGF6	O75095	877
WRAP73	ZBTB40	Q9NUA8	826
WRAP73	SSX2IP	Q9Y2D8	648
WRAP73	CD3D	P04234	633
WRAP73	DNAJC7	Q99615	547
WRAP73	TPRG1L	Q5T0D9	541
WRAP73	NEDD1	Q8NHV4	531
WRAP73	PUM2	Q8TB72	497
WRAP73	TNFRSF1B	P20333	496
WRAP73	WDR81	Q562E7	484
WRAP73	CELF1	Q92879	481
WRAP73	KIFC1	Q9BW19	476
WRAP73	DDX51	Q8N8A6	471
WRAP73	PUM1	Q14671	468
WRAP73	TUBGCP2	Q9BSJ2	467

IntAct

143 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
WRAP73	CEP135	psi-mi:“MI:0914”(association)	0.890
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
WRAP73	SSX2IP	psi-mi:“MI:0915”(physical association)	0.860
WRAP73	SSX2IP	psi-mi:“MI:0403”(colocalization)	0.860
SSX2IP	WRAP73	psi-mi:“MI:0915”(physical association)	0.860
OSBPL9	VAPB	psi-mi:“MI:0914”(association)	0.790
WRAP73	Cep135	psi-mi:“MI:0403”(colocalization)	0.700
ENTREP1	NEDD4	psi-mi:“MI:0914”(association)	0.690
WRAP73	NUDC	psi-mi:“MI:0915”(physical association)	0.560
CEP135	SPICE1	psi-mi:“MI:0914”(association)	0.540
WRAP73	Ssx2ip	psi-mi:“MI:0915”(physical association)	0.540
WRAP73	Ssx2ip	psi-mi:“MI:0403”(colocalization)	0.540
DNAJA1	DNAJA2	psi-mi:“MI:0914”(association)	0.530
KIAA0753	OFD1	psi-mi:“MI:2364”(proximity)	0.480
SSX2IP	SPICE1	psi-mi:“MI:0914”(association)	0.420
AHI1	OFD1	psi-mi:“MI:2364”(proximity)	0.420
WRAP73	cep135	psi-mi:“MI:0915”(physical association)	0.400
Cep135	CEP135	psi-mi:“MI:0915”(physical association)	0.400
Cep135		psi-mi:“MI:0914”(association)	0.350
OFD1	CCDC14	psi-mi:“MI:0914”(association)	0.350
CEP135	TBC1D31	psi-mi:“MI:0914”(association)	0.350
PCM1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
CEP162	IPO5	psi-mi:“MI:0914”(association)	0.350
CEP135	AIMP1	psi-mi:“MI:0914”(association)	0.350
SSX2IP	IPO7	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
WRAP73	AKAP8	psi-mi:“MI:0914”(association)	0.350
WRAP73	Fmnl2	psi-mi:“MI:0914”(association)	0.350

BioGRID (183): WRAP73 (Affinity Capture-MS), WRAP73 (Affinity Capture-MS), WRAP73 (Affinity Capture-MS), SPEN (Affinity Capture-MS), QRICH1 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), RBM12 (Affinity Capture-MS), CEP135 (Affinity Capture-MS), SSSCA1 (Affinity Capture-MS), HDDC3 (Affinity Capture-MS), SDCBP (Affinity Capture-MS), DNAJB4 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), RNF219 (Affinity Capture-MS)

ESM2 similar proteins: A0A4X1TB62, A5D7H2, A7MB16, F1Q8X5, O14562, O35841, O42611, P0C606, P23116, P54198, P55884, P58405, P79987, Q13033, Q13112, Q14152, Q15542, Q1JU68, Q4G061, Q569Z1, Q5E9L7, Q5KU39, Q5R644, Q5R660, Q5R7U7, Q61666, Q676U5, Q6NYU2, Q6PCR7, Q8BHL5, Q8C092, Q8CBY8, Q8JZQ9, Q8QFR2, Q8VHE0, Q91W86, Q96ES7, Q96KG9, Q9BZZ5, Q9D0N7

Diamond homologs: Q9JM98, Q9P2S5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 147 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Loss of Nlp from mitotic centrosomes	10	16.0×	8e-08
Loss of proteins required for interphase microtubule organization from the centrosome	10	16.0×	8e-08
AURKA Activation by TPX2	10	15.4×	8e-08
Anchoring of the basal body to the plasma membrane	13	14.8×	2e-09
Degradation of DVL	6	14.4×	2e-04
DNA Damage Recognition in GG-NER	5	14.4×	1e-03
Regulation of PLK1 Activity at G2/M Transition	11	14.1×	8e-08
Recruitment of mitotic centrosome proteins and complexes	10	13.7×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	7	39.8×	1e-07
protein folding	11	8.8×	1e-05
cilium assembly	15	8.6×	1e-07
proteasome-mediated ubiquitin-dependent protein catabolic process	10	4.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	93
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2201 predictions. Top by Δscore:

Variant	Effect	Δscore
1:3631460:GCTTA:G	donor_loss	1.0000
1:3631461:CTTA:C	donor_loss	1.0000
1:3631462:TTA:T	donor_loss	1.0000
1:3631463:TA:T	donor_loss	1.0000
1:3631464:A:AT	donor_loss	1.0000
1:3632630:G:C	donor_gain	1.0000
1:3633394:TTAC:T	donor_loss	1.0000
1:3633396:A:AC	donor_gain	1.0000
1:3633396:A:T	donor_loss	1.0000
1:3633397:C:CT	donor_gain	1.0000
1:3633397:CA:C	donor_gain	1.0000
1:3634993:TTA:T	donor_loss	1.0000
1:3634994:TA:T	donor_loss	1.0000
1:3634995:A:AC	donor_gain	1.0000
1:3634995:ACTAT:A	donor_gain	1.0000
1:3634996:C:A	donor_loss	1.0000
1:3634996:C:CC	donor_gain	1.0000
1:3634996:CT:C	donor_gain	1.0000
1:3634996:CTA:C	donor_gain	1.0000
1:3634996:CTAT:C	donor_gain	1.0000
1:3634996:CTATC:C	donor_gain	1.0000
1:3635073:ACCT:A	acceptor_loss	1.0000
1:3635075:C:CA	acceptor_loss	1.0000
1:3635076:T:G	acceptor_loss	1.0000
1:3635163:T:A	donor_gain	1.0000
1:3636989:CCTTA:C	donor_loss	1.0000
1:3636990:CTTA:C	donor_loss	1.0000
1:3636991:TTA:T	donor_loss	1.0000
1:3636992:TACC:T	donor_loss	1.0000
1:3636993:A:AT	donor_loss	1.0000

AlphaMissense

2994 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:3631565:A:G	W381R	0.999
1:3631565:A:T	W381R	0.999
1:3638807:A:G	W119R	0.999
1:3638807:A:T	W119R	0.999
1:3638809:A:T	V118D	0.999
1:3646710:A:G	W99R	0.999
1:3646710:A:T	W99R	0.999
1:3647464:A:G	W56R	0.999
1:3647464:A:T	W56R	0.999
1:3635207:A:G	W231R	0.998
1:3635207:A:T	W231R	0.998
1:3637039:C:G	D158H	0.998
1:3631508:A:G	W400R	0.997
1:3631508:A:T	W400R	0.997
1:3635991:A:G	W186R	0.997
1:3635991:A:T	W186R	0.997
1:3646685:A:G	L107P	0.997
1:3646705:G:C	S100R	0.997
1:3646705:G:T	S100R	0.997
1:3646707:T:G	S100R	0.997
1:3646745:A:T	I87K	0.997
1:3646781:A:T	V75D	0.997
1:3647529:C:G	R34P	0.997
1:3635172:G:C	S242R	0.996
1:3635172:G:T	S242R	0.996
1:3635174:T:G	S242R	0.996
1:3637053:C:G	R153P	0.996
1:3638804:A:G	S120P	0.996
1:3638818:C:G	R115P	0.996
1:3646745:A:C	I87R	0.996

dbSNP variants (sampled 300 via entrez): RS1000131167 (1:3633905 C>T), RS1000133295 (1:3638839 G>A,C), RS1000208317 (1:3634100 C>A), RS1000228376 (1:3635517 C>T), RS1000239551 (1:3641081 A>C,G,T), RS1000246665 (1:3650189 T>A,C,G), RS1000484213 (1:3639022 T>C), RS1000689840 (1:3640780 C>T), RS1000842452 (1:3649020 A>G), RS1000942548 (1:3642418 T>C), RS1000979190 (1:3646829 C>A), RS1001055339 (1:3642781 G>T), RS1001170028 (1:3648733 C>T), RS1001240631 (1:3642316 A>G), RS1001468655 (1:3631878 C>G,T)

Disease associations

OMIM: gene MIM:606040 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
anterior segment dysgenesis	Moderate	Autosomal recessive

Mondo (1): anterior segment dysgenesis (MONDO:0019503)

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

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	2
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
sodium arsenite	decreases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression	1
Fonofos	increases methylation	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Lead	affects splicing	1
Methyl Methanesulfonate	increases expression	1
Parathion	increases methylation	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Paclitaxel	affects response to substance	1
1-Butanol	affects cotreatment, increases abundance, increases expression	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KU21	HeLa SilenciX WDR8	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05641103	Not specified	COMPLETED	PREDIGA 2: Spanish Acronym of Educational and Diagnostic Project for Gaucher and ASMD