WDR19

Summary

WDR19 (WD repeat domain 19, HGNC:18340) is a protein-coding gene on chromosome 4p14, encoding WD repeat-containing protein 19 (Q8NEZ3). As component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in cilia function and/or assembly.

The protein encoded by this gene is a member of the WD (tryptophan-aspartic acid) repeat family, which is a large family of structurally-related proteins known to participate in a wide range of cellular processes. Each WD repeat typically contains about 40 amino acids that are usually bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides. This protein contains six WD repeats, three transmembrane domains, and a clathrin heavy-chain repeat. Mutations in this gene have been described in individuals with a wide range of disorders affecting function of the cilium. These disorders are known as ciliopathies, and include Jeune syndrome, Sensenbrenner syndromes, Senior-Loken syndrome, combined or isolated nephronophthisis (NPHP), and retinitis pigmentosa (RP). Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 57728 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +8 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,361 total — 61 pathogenic, 63 likely-pathogenic
• Phenotypes (HPO): 128
• MANE Select transcript: NM_025132

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18340
Approved symbol	WDR19
Name	WD repeat domain 19
Location	4p14
Locus type	gene with protein product
Status	Approved
Aliases	Pwdmp, KIAA1638, FLJ23127, ORF26, DYF-2, Oseg6, IFT144, NPHP13, FAP66, CFAP66
Ensembl gene	ENSG00000157796
Ensembl biotype	protein_coding
OMIM	608151
Entrez	57728

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 8 protein_coding, 7 retained_intron, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000399820, ENST00000502389, ENST00000502718, ENST00000503697, ENST00000503733, ENST00000505055, ENST00000506503, ENST00000506869, ENST00000507228, ENST00000509560, ENST00000510315, ENST00000511729, ENST00000512095, ENST00000512112, ENST00000512448, ENST00000512534, ENST00000512588, ENST00000515631, ENST00000867846, ENST00000867847, ENST00000919861, ENST00000959578

RefSeq mRNA: 2 — MANE Select: NM_025132 NM_001317924, NM_025132

CCDS: CCDS47042

Canonical transcript exons

ENST00000399820 — 37 exons

Exon	Start	End
ENSE00001035092	39194544	39194659
ENSE00002058280	39285487	39285810
ENSE00003468307	39244470	39244552
ENSE00003470220	39189656	39189781
ENSE00003479750	39228486	39228690
ENSE00003498369	39185726	39185817
ENSE00003508378	39186539	39186604
ENSE00003508502	39245369	39245452
ENSE00003513039	39215841	39216013
ENSE00003522202	39253906	39254030
ENSE00003522702	39277020	39277143
ENSE00003528759	39253146	39253292
ENSE00003537519	39278131	39278207
ENSE00003539935	39182529	39182563
ENSE00003540837	39214601	39214671
ENSE00003544528	39217134	39217240
ENSE00003546689	39232162	39232272
ENSE00003547258	39240277	39240334
ENSE00003554087	39205154	39205266
ENSE00003563781	39272980	39273061
ENSE00003576479	39231797	39231956
ENSE00003593942	39269976	39270100
ENSE00003624519	39217983	39218105
ENSE00003627571	39199478	39199593
ENSE00003629697	39267995	39268091
ENSE00003635012	39244248	39244388
ENSE00003656127	39228210	39228357
ENSE00003667295	39278539	39278663
ENSE00003673147	39255848	39255960
ENSE00003678905	39257486	39257554
ENSE00003679818	39216096	39216210
ENSE00003680929	39266063	39266140
ENSE00003682032	39274808	39274958
ENSE00003683516	39205563	39205736
ENSE00003687484	39224884	39225033
ENSE00003691780	39234766	39234875
ENSE00003788860	39203642	39203722

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 98.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0329 / max 364.3632, expressed in 1686 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47365	10.9909	1684
203143	0.0419	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.28	gold quality
bronchial epithelial cell	CL:0002328	97.11	gold quality
adenohypophysis	UBERON:0002196	96.90	gold quality
pituitary gland	UBERON:0000007	96.43	gold quality
left ovary	UBERON:0002119	96.23	gold quality
epithelium of bronchus	UBERON:0002031	96.12	gold quality
right ovary	UBERON:0002118	95.98	gold quality
cerebellar hemisphere	UBERON:0002245	95.90	gold quality
left lobe of thyroid gland	UBERON:0001120	95.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.74	gold quality
cerebellar cortex	UBERON:0002129	95.72	gold quality
calcaneal tendon	UBERON:0003701	95.60	gold quality
right lobe of thyroid gland	UBERON:0001119	95.51	gold quality
bronchus	UBERON:0002185	95.18	gold quality
thyroid gland	UBERON:0002046	95.08	gold quality
endocervix	UBERON:0000458	95.07	gold quality
body of uterus	UBERON:0009853	94.95	gold quality
mucosa of stomach	UBERON:0001199	94.92	gold quality
tibial nerve	UBERON:0001323	94.43	gold quality
right lung	UBERON:0002167	94.16	gold quality
cerebellum	UBERON:0002037	94.09	gold quality
metanephros cortex	UBERON:0010533	93.87	gold quality
ovary	UBERON:0000992	93.38	gold quality
ascending aorta	UBERON:0001496	93.28	gold quality
thoracic aorta	UBERON:0001515	93.13	gold quality
right frontal lobe	UBERON:0002810	92.95	gold quality
descending thoracic aorta	UBERON:0002345	92.84	gold quality
left uterine tube	UBERON:0001303	92.77	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.45	gold quality
ventricular zone	UBERON:0003053	92.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting WDR19, 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-574-5P	100.00	66.01	989
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-3664-3P	97.85	67.62	1452

Literature-anchored findings (GeneRIF, showing 12)

• Expressed in normal and neoplastic prostate epithelium and is regulated by androgenic hormones. (PMID:12906858)
• Overexpression of WDR19 is associated with prostate cancer (PMID:18316561)
• Ciliopathies with skeletal anomalies and renal insufficiency due to mutations in the IFT-A gene WDR19 (PMID:22019273)
• Mutations in WDR19 gene is associated with Caroli disease. (PMID:23559409)
• WDR19: an ancient, retrograde, intraflagellar ciliary protein is mutated in autosomal recessive retinitis pigmentosa and in Senior-Loken syndrome. (PMID:23683095)
• WDR19 mutations can cause a broad spectrum of ciliopathies that extends to Jeune and Sensenbrenner syndromes, RP and renal NPHP-like phenotypes (PMID:24504730)
• Nephronophthisis 13 (Autosomal Recessive Polycystic Kidney Disease) is associated with mutations in the WDR19 gene.Caroli disease is a major extra-renal phenotype associated with mutations in WDR19 in the Korean population. (PMID:25726036)
• Case Reports: that WDR19 mutations can cause dysplastic kidney in addition to nephronophthisis in infants with Sensenbrenner syndrome. (PMID:28621010)
• A novel homozygous mutation in WDR19 induces disorganization of microtubules in sperm flagella and nonsyndromic asthenoteratospermia. (PMID:32323121)
• Molecular basis of ciliary defects caused by compound heterozygous IFT144/WDR19 mutations found in cranioectodermal dysplasia. (PMID:33517396)
• Stargardt-like Clinical Characteristics and Disease Course Associated with Variants in the WDR19 Gene. (PMID:36833218)
• Identification of the primary ciliary proteins IFT38 and IFT144 to enhance serum-mediated YAP activation and cell proliferation. (PMID:37783116)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wdr19	ENSDARG00000037406
mus_musculus	Wdr19	ENSMUSG00000037890
rattus_norvegicus	Wdr19	ENSRNOG00000002932
drosophila_melanogaster	Oseg6	FBGN0034452
caenorhabditis_elegans		WBGENE00001118

Protein

Protein identifiers

WD repeat-containing protein 19 — Q8NEZ3 (reviewed: Q8NEZ3)

Alternative names: Intraflagellar transport 144 homolog

All UniProt accessions (8): D6R9P6, D6RAI4, D6RBA0, D6RCF7, D6RE75, D6RIE4, Q8NEZ3, H0Y8K9

UniProt curated annotations — full annotation on UniProt →

Function. As component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in cilia function and/or assembly. Essential for functional IFT-A assembly and ciliary entry of GPCRs. Associates with the BBSome complex to mediate ciliary transport.

Subunit / interactions. Component of the IFT complex A (IFT-A) complex. IFT-A complex is divided into a core subcomplex composed of IFT122:IFT140:WDR19 which is associated with TULP3 and a peripheral subcomplex composed of IFT43:WDR35:TTC21B. Interacts (via C-terminal region) with IFT122 (via C-terminal region). Interacts with BBS1. Interacts with TTC25.

Subcellular location. Cell projection. Cilium. Cytoplasm. Cytoskeleton. Cilium basal body. Photoreceptor outer segment. Flagellum.

Tissue specificity. Some isoforms are tissue-specific. Highly expressed in the prostate. Lower expression in the cerebellum, pituitary gland, fetal lung, and pancreas. In normal prostate, expressed in both basal and luminal epithelial cells. No expression detected in fibromuscular stromal cells, endothelial cells, or infiltrating lymphocytes. Uniformed expression in prostate adenocarcinoma cells.

Disease relevance. Cranioectodermal dysplasia 4 (CED4) [MIM:614378] A disorder primarily characterized by craniofacial, skeletal and ectodermal abnormalities. Clinical features include craniosynostosis, narrow rib cage, short limbs, brachydactyly, hypoplastic and widely spaced teeth, sparse hair, skin laxity and abnormal nails. Nephronophthisis leading to progressive renal failure, hepatic fibrosis, heart defects, and retinitis pigmentosa have also been described. The disease is caused by variants affecting the gene represented in this entry. Short-rib thoracic dysplasia 5 with or without polydactyly (SRTD5) [MIM:614376] A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a ’trident’ appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. The disease is caused by variants affecting the gene represented in this entry. Nephronophthisis 13 (NPHP13) [MIM:614377] An autosomal recessive disorder resulting in end-stage renal disease. It is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. The disease is caused by variants affecting the gene represented in this entry. Senior-Loken syndrome 8 (SLSN8) [MIM:616307] A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. The disease is caused by variants affecting the gene represented in this entry. Spermatogenic failure 72 (SPGF72) [MIM:619867] An autosomal recessive male infertility disorder characterized by asthenoteratospermia and multiple morphologic abnormalities of the flagella, including coiled, short, angulated, absent, and irregular-caliber flagella, resulting in absent sperm motility. The disease may be caused by variants affecting the gene represented in this entry.

Induction. By androgenic hormones. Expression increased 3-fold in an androgen-stimulated androgen-sensitive prostate adenocarcinoma cell line compared with androgen-deprived cells.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NEZ3-1	1	yes
Q8NEZ3-2	2

RefSeq proteins (2): NP_001304853, NP_079408* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR039468	WDR19_WD40_rpt	Domain
IPR040379	WDR19/dyf-2	Family
IPR056168	TPR_IF140/IFT172/WDR19	Domain
IPR056170	Znf_IFT121-like	Domain
IPR057855	Beta-prop_WDR19_1st	Domain

Pfam: PF15911, PF23145, PF23146, PF23389, PF24762

UniProt features (167 total): strand 67, helix 52, turn 18, repeat 12, sequence variant 12, sequence conflict 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8BBG	ELECTRON MICROSCOPY	3.5
8FGW	ELECTRON MICROSCOPY	3.7
8FH3	ELECTRON MICROSCOPY	4.3
8BBF	ELECTRON MICROSCOPY	8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEZ3-F1	86.44	0.39

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-5620924	Intraflagellar transport

MSigDB gene sets: 448 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, MODULE_255, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, MODULE_317, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, MAYBURD_RESPONSE_TO_L663536_UP, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EAR_DEVELOPMENT

GO Biological Process (21): cell morphogenesis (GO:0000902), in utero embryonic development (GO:0001701), gonad development (GO:0008406), embryonic limb morphogenesis (GO:0030326), embryonic camera-type eye development (GO:0031076), intraciliary retrograde transport (GO:0035721), ear morphogenesis (GO:0042471), receptor clustering (GO:0043113), embryonic cranial skeleton morphogenesis (GO:0048701), nervous system process (GO:0050877), digestive system development (GO:0055123), cilium assembly (GO:0060271), smoothened signaling pathway involved in dorsal/ventral neural tube patterning (GO:0060831), myotome development (GO:0061055), protein-containing complex assembly (GO:0065003), protein localization to ciliary membrane (GO:1903441), smoothened signaling pathway (GO:0007224), dorsal/ventral neural tube patterning (GO:0021904), cell projection organization (GO:0030030), cilium organization (GO:0044782), protein localization to membrane (GO:0072657)

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

GO Cellular Component (11): photoreceptor outer segment (GO:0001750), plasma membrane (GO:0005886), cilium (GO:0005929), intraciliary transport particle A (GO:0030991), motile cilium (GO:0031514), photoreceptor connecting cilium (GO:0032391), ciliary tip (GO:0097542), non-motile cilium (GO:0097730), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Hedgehog	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cilium	3
protein localization to membrane	2
protein localization to cilium	2
photoreceptor cell cilium	2
intraciliary transport particle	2
anatomical structure morphogenesis	1
chordate embryonic development	1
development of primary sexual characteristics	1
animal organ development	1
reproductive structure development	1
limb morphogenesis	1
embryonic appendage morphogenesis	1
camera-type eye development	1
embryonic organ development	1
intraciliary transport	1
ear development	1
embryonic organ morphogenesis	1
sensory organ morphogenesis	1
plasma membrane	1
embryonic skeletal system morphogenesis	1
cranial skeletal system development	1
system process	1
system development	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
smoothened signaling pathway	1
dorsal/ventral neural tube patterning	1
anatomical structure development	1
somite development	1
cellular component assembly	1
protein-containing complex organization	1
protein localization to cell periphery	1
cell surface receptor signaling pathway	1
dorsal/ventral pattern formation	1

Protein interactions and networks

STRING

1134 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR19	IFT43	Q96FT9	997
WDR19	WDR35	Q9P2L0	997
WDR19	IFT140	Q96RY7	997
WDR19	TTC21B	Q7Z4L5	994
WDR19	IFT122	Q9HBG6	992
WDR19	IFT80	Q9P2H3	845
WDR19	IFT172	Q9UG01	841
WDR19	IFT52	Q9Y366	816
WDR19	CLTCL1	P53675	785
WDR19	BBS1	Q8NFJ9	784
WDR19	IFT22	Q9H7X7	781
WDR19	IFT46	Q9NQC8	774
WDR19	IFT88	Q13099	771
WDR19	IFT56	A0AVF1	770
WDR19	IFT81	Q8WYA0	768

IntAct

66 interactions, top by confidence:

A	B	Type	Score
WDR19	TULP3	psi-mi:“MI:0914”(association)	0.860
TULP3	WDR19	psi-mi:“MI:0915”(physical association)	0.860
TULP3	WDR19	psi-mi:“MI:0914”(association)	0.860
TULP3	TTC21B	psi-mi:“MI:0914”(association)	0.840
TTC21B	TULP3	psi-mi:“MI:0914”(association)	0.840
IFT122	WDR19	psi-mi:“MI:0914”(association)	0.800
IFT122	WDR19	psi-mi:“MI:0915”(physical association)	0.800
WDR19	IFT122	psi-mi:“MI:0915”(physical association)	0.800
TULP3	FOXK2	psi-mi:“MI:0914”(association)	0.790
IFT43	TULP3	psi-mi:“MI:0914”(association)	0.790
IFT140	WDR19	psi-mi:“MI:0915”(physical association)	0.780
WDR19	IFT140	psi-mi:“MI:0915”(physical association)	0.780
IFT140	WDR19	psi-mi:“MI:0914”(association)	0.780
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
IFTAP	PLK1	psi-mi:“MI:0914”(association)	0.640
TULP3	GGPS1	psi-mi:“MI:0914”(association)	0.640
IFT43	TTC21B	psi-mi:“MI:0914”(association)	0.530
TKT	POTEF	psi-mi:“MI:0914”(association)	0.530
IFT122	DNAJA2	psi-mi:“MI:0914”(association)	0.530
TULP3	HSPG2	psi-mi:“MI:0914”(association)	0.530
IFTAP	WDR19	psi-mi:“MI:0914”(association)	0.530
TULP2	LONP1	psi-mi:“MI:0914”(association)	0.530

BioGRID (51): WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR19 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8EXB5, A4QNE6, A8WGF4, C1BK83, O35142, O43684, O55029, P35605, P35606, Q17QU5, Q1JP79, Q1JQB2, Q29RH4, Q29RZ9, Q3UGF1, Q4FZW5, Q4R4I8, Q561Y0, Q5I0B4, Q5M7F6, Q5MNZ6, Q5R664, Q5RB58, Q5U4Y8, Q5VQ78, Q6GNF1, Q6NWV3, Q6PA72, Q6TGU2, Q803V5, Q8AVT9, Q8BGF3, Q8IWZ6, Q8K2G4, Q8L828, Q8NEZ3, Q8VE80, Q92747, Q96J01, Q96MX6

Diamond homologs: A0A1L8I2C5, A0A396ISC0, A3LQ86, D3Z3I0, F4K5R6, O13286, O94411, O94423, O94620, P25387, P26309, P53197, P78972, Q09786, Q12834, Q15269, Q3E906, Q4PSE4, Q54KM3, Q54MZ3, Q5H7C0, Q5RFQ3, Q62623, Q86Y33, Q8L3Z8, Q8LPL5, Q8NEZ3, Q8VZS9, Q93134, Q9JJ66, Q9M7I2, Q9P783, Q9R1K5, Q9S7H3, Q9S7I8, Q9SZA4, Q9UM11, G5ECZ4, Q3UGF1, A3LTS5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WDR19	“form complex”	“ITF complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 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
Intraflagellar transport	5	30.4×	9e-05
Hedgehog ‘off’ state	5	27.0×	9e-05

GO biological processes:

GO term	Partners	Fold	FDR
intraciliary retrograde transport	5	144.0×	5e-08
protein localization to cilium	6	61.7×	8e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

1361 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	61
Likely pathogenic	63
Uncertain significance	616
Likely benign	444
Benign	54

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068591	NM_025132.4(WDR19):c.2351_2361del (p.Gln784fs)	Pathogenic
1071241	NM_025132.4(WDR19):c.388C>T (p.Arg130Ter)	Pathogenic
1073132	NM_025132.4(WDR19):c.1911_1914del (p.Phe637fs)	Pathogenic
127154	NM_025132.4(WDR19):c.641dup (p.Leu214fs)	Pathogenic
127156	NM_025132.4(WDR19):c.682C>T (p.Gln228Ter)	Pathogenic
1347795	NM_025132.4(WDR19):c.3184-2A>G	Pathogenic
1401950	NM_025132.4(WDR19):c.2481dup (p.Arg828fs)	Pathogenic
1446760	NM_025132.4(WDR19):c.632dup (p.Leu211fs)	Pathogenic
1454330	NC_000004.11:g.(?39184178)(39184203_?)del	Pathogenic
1456271	NM_025132.4(WDR19):c.234C>A (p.Cys78Ter)	Pathogenic
1457671	NC_000004.11:g.(?39257448)(39257600_?)del	Pathogenic
1686921	NM_025132.4(WDR19):c.1483G>T (p.Gly495Cys)	Pathogenic
1686922	NM_025132.4(WDR19):c.1853T>C (p.Leu618Pro)	Pathogenic
1686923	NM_025132.4(WDR19):c.956del (p.Asn319fs)	Pathogenic
1686924	NM_025132.4(WDR19):c.2645+1G>T	Pathogenic
1686927	NM_025132.4(WDR19):c.3811A>G (p.Lys1271Glu)	Pathogenic
189379	NM_025132.4(WDR19):c.203T>A (p.Val68Asp)	Pathogenic
189380	NM_025132.4(WDR19):c.407-2A>G	Pathogenic
2011472	NM_025132.4(WDR19):c.3457del (p.Ile1153fs)	Pathogenic
2023838	NM_025132.4(WDR19):c.2337del (p.Glu780fs)	Pathogenic
2041533	NM_025132.4(WDR19):c.526C>T (p.Gln176Ter)	Pathogenic
2052921	NM_025132.4(WDR19):c.422_423del (p.Arg141fs)	Pathogenic
2087751	NM_025132.4(WDR19):c.2972del (p.Asn991fs)	Pathogenic
2090526	NM_025132.4(WDR19):c.2589T>G (p.Tyr863Ter)	Pathogenic
2102299	NM_025132.4(WDR19):c.697_701dup (p.Val235fs)	Pathogenic
2104717	NM_025132.4(WDR19):c.2797del (p.Asp933fs)	Pathogenic
2148838	NM_025132.4(WDR19):c.812del (p.Ala271fs)	Pathogenic
2174208	NM_025132.4(WDR19):c.749C>G (p.Ser250Ter)	Pathogenic
2426916	NC_000004.11:g.(?39216201)(39218880_?)del	Pathogenic
2426917	NC_000004.11:g.(?39218734)(39219745_?)del	Pathogenic

SpliceAI

5921 predictions. Top by Δscore:

Variant	Effect	Δscore
4:39185724:A:AG	acceptor_gain	1.0000
4:39185725:G:GG	acceptor_gain	1.0000
4:39185725:GC:G	acceptor_gain	1.0000
4:39185725:GCGT:G	acceptor_gain	1.0000
4:39185816:GG:G	donor_gain	1.0000
4:39185817:GG:G	donor_gain	1.0000
4:39186537:A:AG	acceptor_gain	1.0000
4:39186538:G:GG	acceptor_gain	1.0000
4:39186538:GA:G	acceptor_gain	1.0000
4:39186538:GAGCT:G	acceptor_gain	1.0000
4:39186603:GG:G	donor_gain	1.0000
4:39186604:GG:G	donor_gain	1.0000
4:39186605:G:GG	donor_gain	1.0000
4:39189651:A:AG	acceptor_gain	1.0000
4:39189652:A:G	acceptor_gain	1.0000
4:39189654:A:AG	acceptor_gain	1.0000
4:39189655:G:GA	acceptor_gain	1.0000
4:39189655:GT:G	acceptor_gain	1.0000
4:39189778:TGAGG:T	donor_loss	1.0000
4:39189779:GAG:G	donor_gain	1.0000
4:39189780:AGGTA:A	donor_loss	1.0000
4:39189782:G:A	donor_loss	1.0000
4:39189783:T:A	donor_loss	1.0000
4:39203638:TTA:T	acceptor_loss	1.0000
4:39203639:TA:T	acceptor_loss	1.0000
4:39203640:A:AG	acceptor_gain	1.0000
4:39203641:G:GA	acceptor_gain	1.0000
4:39203641:GA:G	acceptor_gain	1.0000
4:39203641:GAC:G	acceptor_gain	1.0000
4:39203641:GACA:G	acceptor_gain	1.0000

AlphaMissense

8936 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:39189675:T:A	W62R	0.998
4:39189675:T:C	W62R	0.998
4:39245428:C:A	A902D	0.998
4:39244482:G:C	A859P	0.997
4:39244486:C:A	A860D	0.997
4:39253288:G:C	A958P	0.997
4:39253950:T:C	L974P	0.997
4:39189677:G:C	W62C	0.996
4:39189677:G:T	W62C	0.996
4:39194591:C:A	A113D	0.996
4:39199510:T:A	W147R	0.996
4:39199510:T:C	W147R	0.996
4:39199564:A:C	S165R	0.996
4:39199566:T:A	S165R	0.996
4:39199566:T:G	S165R	0.996
4:39205718:C:A	A291D	0.996
4:39215858:T:A	W327R	0.996
4:39215858:T:C	W327R	0.996
4:39216130:C:A	P390H	0.996
4:39228267:T:A	W563R	0.996
4:39228267:T:C	W563R	0.996
4:39253156:G:C	A914P	0.996
4:39253289:C:A	A958D	0.996
4:39253937:G:C	A970P	0.996
4:39253938:C:A	A970D	0.996
4:39253989:C:A	A987D	0.996
4:39255887:C:A	A1014D	0.996
4:39266100:T:C	L1074P	0.996
4:39189700:C:A	A70E	0.995
4:39218089:T:C	L488P	0.995

dbSNP variants (sampled 300 via entrez): RS1000008851 (4:39186406 G>A,T), RS1000119063 (4:39248697 T>G), RS1000127984 (4:39228964 G>A,T), RS1000133208 (4:39285042 G>A), RS1000147371 (4:39267119 A>G), RS1000155302 (4:39267539 A>G), RS1000166770 (4:39192657 C>T), RS1000219807 (4:39270657 C>T), RS1000224296 (4:39228473 T>C), RS1000226637 (4:39220831 T>TTATG), RS1000241823 (4:39193685 C>G,T), RS1000290532 (4:39221580 G>A), RS1000298874 (4:39278335 C>T), RS10003834 (4:39252156 C>T), RS1000400434 (4:39235161 C>T)

Disease associations

OMIM: gene MIM:608151 | disease phenotypes: MIM:614376, MIM:614377, MIM:614378, MIM:616307, MIM:619867, MIM:268000, MIM:218330, MIM:204000, MIM:208500, MIM:266900, MIM:209900, MIM:269860, MIM:123100, MIM:256100, MIM:266920

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliopathy	Definitive	Autosomal recessive
asphyxiating thoracic dystrophy 5	Definitive	Autosomal recessive
cranioectodermal dysplasia 4	Definitive	Autosomal recessive
nephronophthisis 13	Strong	Autosomal recessive
Senior-Loken syndrome 8	Strong	Autosomal recessive
cranioectodermal dysplasia	Supportive	Autosomal recessive
Senior-Loken syndrome	Supportive	Autosomal recessive
Jeune syndrome	Supportive	Autosomal recessive
nephronophthisis 1	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
ciliopathy	Definitive	AR

Mondo (23): asphyxiating thoracic dystrophy 5 (MONDO:0013717), nephronophthisis 13 (MONDO:0013718), cranioectodermal dysplasia 4 (MONDO:0013719), Senior-Loken syndrome 8 (MONDO:0014579), spermatogenic failure 72 (MONDO:0030809), retinitis pigmentosa (MONDO:0019200), cone dystrophy (MONDO:0000455), cranioectodermal dysplasia (MONDO:0009032), Leber congenital amaurosis (MONDO:0018998), connective tissue disorder (MONDO:0003900), Jeune syndrome (MONDO:0018770), inherited retinal dystrophy (MONDO:0019118), Senior-Loken syndrome (MONDO:0017842), optic atrophy (MONDO:0003608), intellectual disability (MONDO:0001071)

Orphanet (14): Cranioectodermal dysplasia (Orphanet:1515), Senior-Loken syndrome (Orphanet:3156), Jeune syndrome (Orphanet:474), Nephronophthisis (Orphanet:655), Retinitis pigmentosa (Orphanet:791), Progressive cone dystrophy (Orphanet:1871), Leber congenital amaurosis (Orphanet:65), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Bardet-Biedl syndrome (Orphanet:110), Ciliopathy (Orphanet:363250), Short rib-polydactyly syndrome, Beemer-Langer type (Orphanet:93268), Craniosynostosis (Orphanet:1531), Saldino-Mainzer syndrome (Orphanet:140969), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

128 total (30 of 128 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000090	Nephronophthisis
HP:0000093	Proteinuria
HP:0000096	Glomerular sclerosis
HP:0000099	Glomerulonephritis
HP:0000112	Nephropathy
HP:0000164	Abnormality of the dentition
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000233	Thin vermilion border
HP:0000268	Dolichocephaly
HP:0000269	Prominent occiput
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000319	Smooth philtrum
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000529	Progressive visual loss
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000556	Retinal dystrophy
HP:0000601	Hypotelorism
HP:0000639	Nystagmus

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002386_18	Cognitive function	6.000000e-07
GCST009310_34	Sensorimotor dexterity	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003925	cognition
EFO:0008354	cognitive function measurement

MeSH disease descriptors (14)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D000077765	Cone Dystrophy	C11.270.151; C11.768.216
D003240	Connective Tissue Diseases	C17.300
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C537571	Jeune syndrome (supp.)
C537699	Nephronophthisis, familial juvenile (supp.)
C537580	Senior Loken Syndrome (supp.)
C537599	Short rib-polydactyly syndrome, Beemer type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Acetaminophen	increases expression	2
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment	2
Valproic Acid	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Air Pollutants	decreases expression	1
Air Pollutants, Occupational	affects expression	1
Benzo(a)pyrene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Selenium	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_WR22	KSCBi010-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa
NCT01068561	PHASE1	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa