C1QTNF5

Summary

C1QTNF5 (C1q and TNF related 5, HGNC:14344) is a protein-coding gene on chromosome 11q23.3, encoding Complement C1q tumor necrosis factor-related protein 5 (Q9BXJ0).

This gene encodes a member of a family of proteins that function as components of basement membranes and may play a role in cell adhesion. Mutations in this gene have been associated with late-onset retinal degeneration. The protein may be encoded by either a bicistronic transcript including sequence from the upstream membrane frizzled-related protein gene (MFRP), or by a monocistronic transcript expressed from an internal promoter.

Source: NCBI Gene 114902 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited retinal dystrophy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 915 total — 46 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_001278431

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14344
Approved symbol	C1QTNF5
Name	C1q and TNF related 5
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	CTRP5, DKFZp586B0621, LORD
Ensembl gene	ENSG00000223953
Ensembl biotype	protein_coding
OMIM	608752
Entrez	114902

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000525657, ENST00000528368, ENST00000530681, ENST00000634633

RefSeq mRNA: 2 — MANE Select: NM_001278431 NM_001278431, NM_015645

CCDS: CCDS8420

Canonical transcript exons

ENST00000528368 — 3 exons

Exon	Start	End
ENSE00002281377	119340695	119340883
ENSE00003482899	119338942	119339848
ENSE00003659348	119340184	119340440

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 94.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4819 / max 126.5995, expressed in 970 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122702	3.5329	864
122703	3.2158	758
122707	0.3890	25
122704	0.3673	224
122701	0.3659	214
122708	0.2176	20
122709	0.0714	14
122710	0.0145	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	94.79	gold quality
gall bladder	UBERON:0002110	94.02	gold quality
ascending aorta	UBERON:0001496	92.81	gold quality
thoracic aorta	UBERON:0001515	92.56	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.94	gold quality
adipose tissue	UBERON:0001013	91.72	gold quality
omental fat pad	UBERON:0010414	91.49	gold quality
metanephros cortex	UBERON:0010533	91.10	gold quality
right coronary artery	UBERON:0001625	91.00	gold quality
mucosa of stomach	UBERON:0001199	90.71	gold quality
tibial artery	UBERON:0007610	90.51	gold quality
popliteal artery	UBERON:0002250	90.48	gold quality
right lung	UBERON:0002167	90.18	gold quality
myometrium	UBERON:0001296	90.17	gold quality
left coronary artery	UBERON:0001626	90.17	gold quality
smooth muscle tissue	UBERON:0001135	89.77	gold quality
right atrium auricular region	UBERON:0006631	89.75	gold quality
upper lobe of left lung	UBERON:0008952	89.70	gold quality
descending thoracic aorta	UBERON:0002345	89.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.57	gold quality
stromal cell of endometrium	CL:0002255	89.50	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.12	gold quality
body of uterus	UBERON:0009853	89.11	gold quality
lower esophagus	UBERON:0013473	89.05	gold quality
endocervix	UBERON:0000458	89.01	gold quality
left uterine tube	UBERON:0001303	88.86	gold quality
lung	UBERON:0002048	88.49	gold quality
right lobe of thyroid gland	UBERON:0001119	88.48	gold quality
heart	UBERON:0000948	88.09	gold quality
thoracic mammary gland	UBERON:0005200	87.85	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS2, HNF4A

miRNA regulators (miRDB)

22 targeting C1QTNF5, 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-513B-5P	99.99	69.96	2150
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-3670	97.88	64.39	763
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-3972	97.19	66.46	808
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-631	97.05	66.93	602
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-3690	96.44	65.18	737
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722
HSA-MIR-4765	93.11	66.17	737

Literature-anchored findings (GeneRIF, showing 39)

• cloning of the bicistronic transcript and characterization of the upstream ORF, MFRP (PMID:11263980)
• CTRP5 has a role in extracellular deposit formation in late-onset retinal degeneration (PMID:12944416)
• A single locus at 11q23 is implicated in a complex ocular phenotype involving RPE and CE, tissues of neuroectodermal origin. (PMID:16123441)
• In this family with a proven mutation in this gene, peripupillary iris atrophy and abnormally long anterior zonular insertions were present before retinal changes and visual loss. (PMID:16376663)
• L-ORMD is due to insufficient levels of secreted C1QTNF5, compromised RPE cell function resulting from ER retention of the mutant protein or both mechanisms. (PMID:16600989)
• C1QTNF5 has a role in late-onset retinal degeneration (PMID:17249553)
• This study revealed the presence of a functional promoter for the CTRP5 gene located 5’ of its start site. (PMID:20554618)
• A physiological function for C1QTNF5 (myonectin) in linking insulin resistance with quantitative changes in mtDNA. (PMID:22031510)
• pathogenic role of C1qtnf5 Ser163Arg mutation (PMID:22110650)
• Late-onset retinal degeneration is a progressive degeneration, and anterior segment abnormalities present early. (PMID:22277927)
• The crystal structure of the trimeric globular domain of human C1QTNF5 at 1.34A resolution reveals unique features of this novel C1q family member. (PMID:22892318)
• C1QTNF5 retinopathy is an autosomal dominant LORD resulting in a complex ocular phenotype involving the RPE and ciliary epithelium. SD-OCT findings revealed widespread photoreceptor loss and diffuse choroidal thinning. (PMID:23289492)
• CTRP-5 might be a novel adipokine that circulates abundantly in human sera. (PMID:23430573)
• C1QTNF5 monomers can multimerize into a bouquet-like octadecamer. (PMID:24531000)
• Late-onset retinal degeneration, proven to have the p.Ser163Arg mutation in C1QTNF5, and asked whether retina-wide sub-RPE deposit was detectable and quantifiable. (PMID:25010528)
• Our results provide the first genetic and physiological evidence for CTRP5 as a negative regulator of glucose metabolism and insulin sensitivity. Inhibition of CTRP5 action may result in the alleviation of insulin resistance associated with obesity and diabetes. (PMID:27143553)
• Sequencing of C1QTNF5 revealed 28 unique variants although none showed a statistically significant association with dt-GA when compared with 1000G individuals. (PMID:27149696)
• In children adipocyte C1QTNF5 expression is already strongly related to the degree of obesity and is associated with obesity-related AT alterations, systemic CTRP5 serum levels as well as circulating markers of metabolic disease and is positively regulated by TNFalpha in vitro (PMID:28239164)
• This study describes the identification and characterisation of three novel pathogenic mutations in C1QTNF5 in order to elucidate disease mechanism in late-onset retinal degeneration. In silico and in vitro characterisation show that these mutations perturb protein folding, assembly or polarity of secretion of C1QTNF5 and, importantly, all appear to destabilise the wildtype protein. (PMID:28939808)
• Exercise training-induced increase in serum CTRP3/5 levels may be associated with the reduction of arterial stiffness in middle-aged and older adults. (PMID:29070503)
• High myonectin expression is associated with Type 2 Diabetes. (PMID:29161407)
• When both wild-type and mutant S163R C1QTNF5 are simultaneously delivered subretinally to mouse RPE cells, the mutant impairs the wild-type protein secretion from the RPE, and both proteins are dispersed toward the basal and lateral RPE membrane. (PMID:29721928)
• CTRP5 is a novel pro-atherogenic cytokine and promotes transcytosis and oxidation of LDL in endothelial cells via up-regulation of 12/15-LOX (PMID:30300788)
• The novel mutations in C1QTNF5 identified here expand the genotypic spectrum of mutations causing late-onset retinal dystrophy. (PMID:30451557)
• considering the role of myonectin in increasing fatty acid uptake, exercise training can play an essential role in decreasing obesity-related diseases and metabolic syndrome; this effect is partly related to the roles of myonectin. (PMID:30894898)
• The results implicate HTRA1 and its interaction with CTRP5 in Late-onset retinal degeneration pathology. (PMID:31385385)
• Implications of C1q/TNF-related protein superfamily in patients with coronary artery disease. (PMID:31965030)
• Evaluation of changing the pattern of CTRP5 and inflammatory markers levels in patients with coronary artery disease and type 2 diabetes mellitus. (PMID:32202952)
• Serum myonectin is increased after laparoscopic sleeve gastrectomy. (PMID:32588645)
• Decreased serum myonectin concentrations in diabetic nephropathy patients. (PMID:32852729)
• Autosomal Dominant Gyrate Atrophy-Like Choroidal Dystrophy Revisited: 45 Years Follow-Up and Association with a Novel C1QTNF5 Missense Variant. (PMID:33669876)
• Association of serum and aqueous humor myonectin concentrations with diabetic retinopathy. (PMID:33785845)
• Longitudinal phenotypic study of late-onset retinal degeneration due to a founder variant c.562C>A p.(Pro188Thr) in the C1QTNF5 gene. (PMID:33949280)
• MASSIVE ADVANCING NONEXUDATIVE TYPE 1 CHOROIDAL NEOVASCULARIZATION IN CTRP5 LATE-ONSET RETINAL DEGENERATION: Longitudinal Findings on Multimodal Imaging and Implications for Age-Related Macular Degeneration. (PMID:33990119)
• AMPK modulation ameliorates dominant disease phenotypes of CTRP5 variant in retinal degeneration. (PMID:34887495)
• Increased serum myonectin and irisin levels with myonectin and FNDC5 expressions in polycystic ovary syndrome: a case control study. (PMID:34907845)
• Upregulation of IL-8, osteonectin, and myonectin mRNAs by intermittent hypoxia via OCT1- and NRF2-mediated mechanisms in skeletal muscle cells. (PMID:36457269)
• Longitudinal Changes of Retinal Structure in Molecularly Confirmed C1QTNF5 Patients With Late-Onset Retinal Degeneration. (PMID:38085246)
• C1QTNF5 is a novel attachment factor that facilitates the entry of influenza A virus. (PMID:38246238)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	c1qtnf5	ENSDARG00000056134
mus_musculus	C1qtnf5	ENSMUSG00000079592
rattus_norvegicus	C1qtnf5	ENSRNOG00000007613

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), C1QL2 (ENSG00000144119), COL8A1 (ENSG00000144810), C1QTNF2 (ENSG00000145861), C1QC (ENSG00000159189), C1QTNF7 (ENSG00000163145), C1QL3 (ENSG00000165985), COL8A2 (ENSG00000171812), C1QTNF4 (ENSG00000172247), C1QB (ENSG00000173369), C1QA (ENSG00000173372), C1QTNF1 (ENSG00000173918), ADIPOQ (ENSG00000181092), OTOL1 (ENSG00000182447), C1QTNF8 (ENSG00000184471), C1QL4 (ENSG00000186897), C1QTNF9B (ENSG00000205863), C1QTNF9 (ENSG00000240654)

Protein

Protein identifiers

Complement C1q tumor necrosis factor-related protein 5 — Q9BXJ0 (reviewed: Q9BXJ0)

All UniProt accessions (3): Q9BXJ0, A0A024R3F8, A0A0U1RQW5

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. May interact with ERFE. Homotrimer (via collagen-like domain). May form higher order oligomers by supercoiling of the trimers.

Subcellular location. Secreted.

Disease relevance. Late-onset retinal degeneration (LORD) [MIM:605670] Autosomal dominant disorder characterized by onset in the fifth to sixth decade with night blindness and punctate yellow-white deposits in the retinal fundus, progressing to severe central and peripheral degeneration, with choroidal neovascularization and chorioretinal atrophy. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. This protein is produced by a bicistronic gene which also produces the MFRP protein from a non-overlapping reading frame.

RefSeq proteins (2): NP_001265360, NP_056460 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001073	C1q_dom	Domain
IPR008160	Collagen	Repeat
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR050392	Collagen/C1q_domain	Family

Pfam: PF00386, PF01391

UniProt features (20 total): strand 10, turn 2, domain 2, sequence variant 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4F3J	X-RAY DIFFRACTION	1.34
4NN0	X-RAY DIFFRACTION	1.42

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXJ0-F1	80.99	0.53

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 93 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOCC_COLLAGEN_TRIMER, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_EAR_DEVELOPMENT, GOBP_SECRETION, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOCC_CELL_CELL_JUNCTION, RGAGGAARY_PU1_Q6, GOCC_APICAL_PART_OF_CELL, GOCC_LATERAL_PLASMA_MEMBRANE, GOCC_ANCHORING_JUNCTION, GOCC_PLASMA_MEMBRANE_REGION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, SMAD_Q6

GO Biological Process (2): protein secretion (GO:0009306), inner ear development (GO:0048839)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (11): collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), apical plasma membrane (GO:0016324), lateral plasma membrane (GO:0016328), transport vesicle (GO:0030133), cell projection (GO:0042995), extracellular region (GO:0005576), membrane (GO:0016020), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
ear development	1
anatomical structure development	1
protein binding	1
binding	1
protein-containing complex	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
apical part of cell	1
plasma membrane region	1
plasma membrane	1
endomembrane system	1
cytoplasmic vesicle	1
cellular_component	1

Protein interactions and networks

STRING

348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1QTNF5	MFRP	Q9BY79	636
C1QTNF5	SYPL2	Q5VXT5	453
C1QTNF5	CLIP2	Q9UDT6	449
C1QTNF5	NOA1	Q8NC60	427
C1QTNF5	PRSS56	P0CW18	373
C1QTNF5	DBNL	P84070	362
C1QTNF5	ERFE	Q4G0M1	351
C1QTNF5	SPAG9	O60271	339
C1QTNF5	RPS23	P39028	339
C1QTNF5	SKAP2	O75563	322
C1QTNF5	ABCB8	Q9NUT2	320
C1QTNF5	SERPINB10	P48595	318
C1QTNF5	COL7A1	Q02388	318
C1QTNF5	PSMA6	P34062	315
C1QTNF5	MTMR1	Q13613	314

IntAct

17 interactions, top by confidence:

A	B	Type	Score
C1QTNF5	MFRP	psi-mi:“MI:0915”(physical association)	0.590
SGTB	C1QTNF5	psi-mi:“MI:0915”(physical association)	0.560
GUCA1A	C1QTNF5	psi-mi:“MI:0915”(physical association)	0.560
SGTA	C1QTNF5	psi-mi:“MI:0915”(physical association)	0.560
C1QTNF5	C1QTNF5	psi-mi:“MI:0407”(direct interaction)	0.560
CDH5	MYO1C	psi-mi:“MI:2364”(proximity)	0.270
GUCA1A	C1QTNF5	psi-mi:“MI:0915”(physical association)	0.000
SGTA	C1QTNF5	psi-mi:“MI:0915”(physical association)	0.000
SGTB	C1QTNF5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): C1QTNF5 (Reconstituted Complex), C1QTNF5 (Two-hybrid), C1QTNF5 (Two-hybrid), C1QTNF5 (Two-hybrid)

ESM2 similar proteins: A1A5X5, A5PKD8, A8T655, A8T677, A8T6A1, D3Z7H8, F1SAM7, O75888, P09531, P34820, P34821, P41273, P42917, P43031, P60827, P98087, Q00973, Q02105, Q17QF9, Q4G0M1, Q5FVH0, Q5RJL6, Q5XIG2, Q641Q3, Q6PGN1, Q6UKI2, Q6UW01, Q76KP1, Q7Z5Y6, Q7Z7M0, Q80W15, Q8BGU2, Q8BJ66, Q8IUK8, Q8K479, Q8N119, Q8R2Z0, Q8VE43, Q8WX77, Q96I82

Diamond homologs: A0A060WQA3, A5PN28, A6NHN0, B2RNN3, O75973, O88992, P02745, P02746, P08125, P0C862, P14106, P14282, P23206, P25067, P25318, P27658, P31720, P31721, P83371, P98085, P98086, Q00780, Q02105, Q03692, Q05306, Q05A80, Q06575, Q06576, Q06577, Q0II24, Q15848, Q2KIU3, Q2KIX7, Q3Y5Z3, Q4ZJM7, Q4ZJM9, Q4ZJN1, Q5E9E3, Q5FVH0, Q5RJ80

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HNF4A	“up-regulates quantity by expression”	C1QTNF5	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	46
Likely pathogenic	17
Uncertain significance	458
Likely benign	314
Benign	22

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069330	NM_031433.4(MFRP):c.666del (p.Thr223fs)	Pathogenic
1070551	NM_031433.4(MFRP):c.313del (p.Leu105fs)	Pathogenic
1071727	NM_031433.4(MFRP):c.1090_1091del (p.Thr364fs)	Pathogenic
1074166	NM_031433.4(MFRP):c.1090_1094del (p.Thr364fs)	Pathogenic
1359963	NM_031433.4(MFRP):c.102C>A (p.Cys34Ter)	Pathogenic
1442130	NM_031433.4(MFRP):c.1408C>T (p.Gln470Ter)	Pathogenic
1452557	NM_031433.4(MFRP):c.431_443dup (p.Ser149fs)	Pathogenic
1458089	NM_031433.4(MFRP):c.287_291del (p.Pro96fs)	Pathogenic
1706425	NM_031433.4(MFRP):c.662_663insT (p.Thr223fs)	Pathogenic
183043	NM_031433.4(MFRP):c.951C>A (p.Tyr317Ter)	Pathogenic
183045	NM_031433.4(MFRP):c.201G>A (p.Trp67Ter)	Pathogenic
1905353	NM_031433.4(MFRP):c.1078G>T (p.Glu360Ter)	Pathogenic
191026	NM_031433.4(MFRP):c.746G>A (p.Trp249Ter)	Pathogenic
2024780	NM_031433.4(MFRP):c.1228_1234del (p.Thr410fs)	Pathogenic
209172	NM_031433.4(MFRP):c.958C>T (p.Gln320Ter)	Pathogenic
2152209	NM_031433.4(MFRP):c.1150del (p.His384fs)	Pathogenic
2194741	NM_031433.4(MFRP):c.1333_1334del (p.Asp445fs)	Pathogenic
2418993	NM_031433.4(MFRP):c.500del (p.Asn167fs)	Pathogenic
2706696	NM_031433.4(MFRP):c.1506_1507del (p.Ser502fs)	Pathogenic
2724828	NM_031433.4(MFRP):c.1124+1G>A	Pathogenic
2780867	NM_031433.4(MFRP):c.909dup (p.Asn304fs)	Pathogenic
2818349	NM_031433.4(MFRP):c.499_500dup (p.Asn167fs)	Pathogenic
2907420	NM_031433.4(MFRP):c.577_578del (p.Ser193fs)	Pathogenic
3698874	NM_031433.4(MFRP):c.754dup (p.Ala252fs)	Pathogenic
3717132	NM_031433.4(MFRP):c.1296del (p.Cys433fs)	Pathogenic
3726413	NM_031433.4(MFRP):c.634dup (p.Leu212fs)	Pathogenic
438224	NM_031433.4(MFRP):c.955C>T (p.Gln319Ter)	Pathogenic
4474	NM_031433.4(MFRP):c.1150dup (p.His384fs)	Pathogenic
4475	NM_031433.4(MFRP):c.523C>T (p.Gln175Ter)	Pathogenic
4476	NM_031433.4(MFRP):c.498del (p.Asn167fs)	Pathogenic

SpliceAI

336 predictions. Top by Δscore:

Variant	Effect	Δscore
11:119340693:ACCC:A	donor_gain	1.0000
11:119340693:ACCCC:A	donor_gain	1.0000
11:119340694:CCCC:C	donor_gain	1.0000
11:119340694:CCCCC:C	donor_gain	1.0000
11:119340720:T:TA	donor_gain	1.0000
11:119340693:AC:A	donor_gain	0.9900
11:119340693:ACC:A	donor_gain	0.9900
11:119340694:CC:C	donor_gain	0.9900
11:119340694:CCC:C	donor_gain	0.9900
11:119340709:C:CA	donor_gain	0.9900
11:119340741:CCGG:C	donor_gain	0.9900
11:119339846:GTCCT:G	acceptor_loss	0.9800
11:119339847:TCCTG:T	acceptor_loss	0.9800
11:119339848:CCTG:C	acceptor_loss	0.9800
11:119339849:C:CA	acceptor_loss	0.9800
11:119339850:T:G	acceptor_loss	0.9800
11:119340690:CTCA:C	donor_loss	0.9800
11:119340691:TCA:T	donor_loss	0.9800
11:119340692:CA:C	donor_loss	0.9800
11:119340694:C:CT	donor_loss	0.9800
11:119340710:C:A	donor_gain	0.9800
11:119340831:C:CA	donor_gain	0.9800
11:119339844:CAGTC:C	acceptor_gain	0.9700
11:119339847:TC:T	acceptor_gain	0.9700
11:119339848:CC:C	acceptor_gain	0.9700
11:119339849:C:CC	acceptor_gain	0.9700
11:119340200:G:A	donor_gain	0.9700
11:119340688:GACTC:G	donor_loss	0.9700
11:119340689:ACTC:A	donor_loss	0.9700
11:119340693:A:AC	donor_gain	0.9700

AlphaMissense

1548 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:119339388:G:C	S225R	1.000
11:119339388:G:T	S225R	1.000
11:119339390:T:G	S225R	1.000
11:119339628:G:C	C145W	1.000
11:119339635:A:G	F143S	1.000
11:119339377:C:T	G229E	0.999
11:119339383:A:G	F227S	0.999
11:119339467:A:G	L199P	0.999
11:119339572:A:G	L164P	0.999
11:119339574:G:C	S163R	0.999
11:119339574:G:T	S163R	0.999
11:119339576:T:G	S163R	0.999
11:119339599:A:T	V155D	0.999
11:119339605:A:G	F153S	0.999
11:119339612:A:C	Y151D	0.999
11:119339618:C:A	G149W	0.999
11:119339629:C:T	C145Y	0.999
11:119339634:G:C	F143L	0.999
11:119339634:G:T	F143L	0.999
11:119339635:A:C	F143C	0.999
11:119339636:A:G	F143L	0.999
11:119339745:G:C	F106L	0.999
11:119339745:G:T	F106L	0.999
11:119339746:A:C	F106C	0.999
11:119339746:A:G	F106S	0.999
11:119339747:A:G	F106L	0.999
11:119339403:G:C	S220R	0.998
11:119339403:G:T	S220R	0.998
11:119339405:T:G	S220R	0.998
11:119339560:A:G	L168P	0.998

dbSNP variants (sampled 300 via entrez): RS1000658864 (11:119347615 G>A), RS1000820928 (11:119345092 C>A,G), RS1001545948 (11:119348105 A>G,T), RS1001972882 (11:119345333 T>G), RS1002011614 (11:119340589 G>A), RS1002147275 (11:119340412 G>A), RS1002433949 (11:119346655 G>A,C), RS1002815720 (11:119343064 C>G,T), RS1003682914 (11:119342062 G>A), RS1003860933 (11:119340470 C>T), RS1003867368 (11:119339197 G>A,T), RS1003948702 (11:119345759 C>A), RS1004893867 (11:119339249 G>A,C,T), RS1005269543 (11:119338748 A>G), RS1005563355 (11:119342179 C>T)

Disease associations

OMIM: gene MIM:608752 | disease phenotypes: MIM:611040, MIM:609549, MIM:605670, MIM:268000, MIM:181500, MIM:600165

GenCC curated gene-disease

Disease	Classification	Inheritance
late-onset retinal degeneration	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
inherited retinal dystrophy	Definitive	AD

Mondo (11): isolated microphthalmia 5 (MONDO:0012605), inherited retinal dystrophy (MONDO:0019118), nanophthalmos 2 (MONDO:0012299), optic atrophy (MONDO:0003608), late-onset retinal degeneration (MONDO:0011579), retinitis pigmentosa (MONDO:0019200), schizophrenia (MONDO:0005090), nanophthalmia (MONDO:0005514), thrombocytopenia (MONDO:0002049), anemia (MONDO:0002280), strabismus (MONDO:0003432)

Orphanet (6): Microphthalmia-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome (Orphanet:251279), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Nanophthalmos (Orphanet:35612), Late-onset retinal degeneration (Orphanet:67042), Retinitis pigmentosa (Orphanet:791), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000556	Retinal dystrophy
HP:0100753	Schizophrenia
HP:0001903	Anemia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002846_2	Lifespan	2.000000e-16
GCST006585_1315	Blood protein levels	6.000000e-18

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D000740	Anemia	C15.378.050
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D013285	Strabismus	C10.292.562.887; C11.590.810
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C565309	Late-Onset Retinal Degeneration (supp.)
C567024	Microphthalmia, Posterior, With Retinitis Pigmentosa, Foveoschisis, And Optic Disc Drusen (supp.)
C563700	Nanophthalmos 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
cobaltous chloride	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases 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_D0N0	UCLi023-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

270 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
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
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
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
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
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
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
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)
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)