AGBL5

Summary

AGBL5 (AGBL carboxypeptidase 5, HGNC:26147) is a protein-coding gene on chromosome 2p23.3, encoding Cytosolic carboxypeptidase-like protein 5 (Q8NDL9). Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins.

This gene encodes a metallocarboxypeptidase involved in protein deglutamylation and a member of the peptidase M14 family of proteins. The encoded protein has been described as a “dual-functional” deglutamylase that can remove glutamate residues from both carboxyl termini and side chains of protein substrates. This deglutamylase activity may be important in antiviral immunity. Mutations in this gene are associated with retinitis pigmentosa.

Source: NCBI Gene 60509 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited retinal dystrophy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 754 total — 26 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 37
• MANE Select transcript: NM_021831

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26147
Approved symbol	AGBL5
Name	AGBL carboxypeptidase 5
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21839, CCP5
Ensembl gene	ENSG00000084693
Ensembl biotype	protein_coding
OMIM	615900
Entrez	60509

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000323064, ENST00000360131, ENST00000421915, ENST00000437006, ENST00000441931, ENST00000451003, ENST00000453161, ENST00000477136, ENST00000487078, ENST00000489683, ENST00000889661, ENST00000889664, ENST00000929583

RefSeq mRNA: 2 — MANE Select: NM_021831 NM_001035507, NM_021831

CCDS: CCDS1732, CCDS42665

Canonical transcript exons

ENST00000360131 — 15 exons

Exon	Start	End
ENSE00000542694	27058400	27058602
ENSE00000732135	27056623	27056792
ENSE00000732217	27057303	27057438
ENSE00001078256	27067494	27067646
ENSE00001078257	27068632	27068744
ENSE00001078261	27051668	27051793
ENSE00001078266	27059190	27059404
ENSE00001868490	27070092	27070618
ENSE00003463198	27069573	27069706
ENSE00003487811	27055075	27055253
ENSE00003522738	27052913	27053173
ENSE00003583626	27053402	27053573
ENSE00003587248	27053896	27054059
ENSE00003589100	27054630	27054807
ENSE00003670223	27055682	27056138

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 98.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5182 / max 372.5962, expressed in 1763 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19307	13.3372	1763
19308	0.1567	56
19314	0.0244	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.97	gold quality
right testis	UBERON:0004534	98.91	gold quality
testis	UBERON:0000473	96.20	gold quality
adult organism	UBERON:0007023	91.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.22	gold quality
lower esophagus	UBERON:0013473	90.20	gold quality
endothelial cell	CL:0000115	89.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.24	gold quality
right uterine tube	UBERON:0001302	89.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.00	gold quality
right adrenal gland	UBERON:0001233	88.97	gold quality
right adrenal gland cortex	UBERON:0035827	88.84	gold quality
left adrenal gland cortex	UBERON:0035825	88.58	gold quality
right coronary artery	UBERON:0001625	88.55	gold quality
stromal cell of endometrium	CL:0002255	88.51	gold quality
left adrenal gland	UBERON:0001234	88.47	gold quality
sperm	CL:0000019	88.06	gold quality
metanephros cortex	UBERON:0010533	87.99	gold quality
male germ cell	CL:0000015	87.81	gold quality
right lobe of thyroid gland	UBERON:0001119	87.77	gold quality
adrenal tissue	UBERON:0018303	87.72	gold quality
left lobe of thyroid gland	UBERON:0001120	87.65	gold quality
mucosa of stomach	UBERON:0001199	87.18	gold quality
cortical plate	UBERON:0005343	87.15	gold quality
adenohypophysis	UBERON:0002196	87.13	gold quality
adrenal gland	UBERON:0002369	87.06	gold quality
left uterine tube	UBERON:0001303	86.96	gold quality
adrenal cortex	UBERON:0001235	86.94	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	7.78
E-ANND-3	yes	5.65
E-MTAB-9543	no	11.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting AGBL5, 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-4283	100.00	66.42	2097
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4520-3P	98.75	66.55	963
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-3664-5P	96.74	66.56	770
HSA-MIR-7160-3P	96.40	64.15	462
HSA-MIR-8083	95.93	67.55	694
HSA-MIR-1296-5P	93.94	67.71	305
HSA-MIR-4281	92.91	63.60	271
HSA-MIR-658	88.20	67.03	178

Literature-anchored findings (GeneRIF, showing 8)

• Our study expands the clinical and allelic spectrum of known Retinal dystrophies genes, and reveals AGBL5, CDH16, and DNAJC17 as novel disease candidates. (PMID:26355662)
• Due to the characteristic Retinitis Pigmentosa phenotype in patients carrying the AGBL5 missense mutation we suggest this gene as a candidate for a new form of autosomal recessively inherited RP (PMID:26720455)
• Homology models indicated destabilization of AGBL5 due to the p.Arg281Cys change. (PMID:27764769)
• The identification of AGBL5 and TTLL5, a previously described RP-associated gene encoding the tubulin tyrosine ligase-like family, member 5 protein, highlights the importance of poly- and deglutamylation in retinal homeostasis. (PMID:27842159)
• WES identified a homozygous frameshift mutation (c.1787_1788del, p.His596Argfs*47) in AGBL5, associated with nonsyndromic RP. (PMID:30925032)
• CCP5 and CCP6 retain CP110 and negatively regulate ciliogenesis. (PMID:37226238)
• Mutations in AGBL5 associated with Retinitis pigmentosa. (PMID:38078364)
• Tubulin code eraser CCP5 binds branch glutamates by substrate deformation. (PMID:39020174)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	agbl5	ENSDARG00000045900
mus_musculus	Agbl5	ENSMUSG00000029165
rattus_norvegicus	Agbl5	ENSRNOG00000008612

Paralogs (5): AGTPBP1 (ENSG00000135049), AGBL3 (ENSG00000146856), AGBL2 (ENSG00000165923), AGBL4 (ENSG00000186094), AGBL1 (ENSG00000273540)

Protein

Protein identifiers

Cytosolic carboxypeptidase-like protein 5 — Q8NDL9 (reviewed: Q8NDL9)

Alternative names: ATP/GTP-binding protein-like 5, Protein deglutamylase CCP5

All UniProt accessions (6): Q8NDL9, C9JCE1, C9JHM6, C9JQG9, C9JTY1, H7C1L5

UniProt curated annotations — full annotation on UniProt →

Function. Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins. Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin. Cleaves alpha- and gamma-linked polyglutamate tubulin side-chain, as well as the branching point glutamate. Also catalyzes the removal of alpha-linked glutamate residues from the carboxy-terminus of alpha-tubulin. Mediates deglutamylation of nucleotidyltransferase CGAS, leading to CGAS antiviral defense response activation.

Subcellular location. Cytoplasm. Cytosol. Nucleus. Cytoskeleton. Spindle. Midbody.

Tissue specificity. Expressed in brain.

Disease relevance. Retinitis pigmentosa 75 (RP75) [MIM:617023] A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP75 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M14 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NDL9-1	1	yes
Q8NDL9-2	2
Q8NDL9-3	3

RefSeq proteins (2): NP_001030584, NP_068603* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000834	Peptidase_M14	Domain
IPR034286	M14_AGBL5-like	Domain
IPR040626	Pepdidase_M14_N	Domain
IPR050821	Cytosolic_carboxypeptidase	Family

Pfam: PF00246, PF18027

Enzyme classification (BRENDA):

• EC 3.4.17.24 — tubulin-glutamate carboxypeptidase (BRENDA: 5 organisms, 60 substrates, 5 inhibitors, 4 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BIOTIN-GLU-GLU	0.15	1
BIOTIN-GLU-GLU-GLU	0.18	1
BIOTIN-GLU-GLU-GLU-GLY-GLU-GLU	0.074	1
BIOTIN-GLU-GLU-GLY-GLU-GLU-GLU	0.076	1

Catalyzed reactions (Rhea), 4 shown:

• (L-glutamyl)(n+1)-gamma-L-glutamyl-L-glutamyl-[protein] + H2O = (L-glutamyl)(n)-gamma-L-glutamyl-L-glutamyl-[protein] + L-glutamate (RHEA:60004)
• gamma-L-glutamyl-L-glutamyl-[protein] + H2O = L-glutamyl-[protein] + L-glutamate (RHEA:60152)
• C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-[tubulin] + H2O = C-terminal L-alpha-aminoacyl-L-glutamyl-[tubulin] + L-glutamate (RHEA:63792)
• C-terminal L-alpha-aminoacyl-L-glutamyl-[tubulin] + H2O = C-terminal L-alpha-aminoacyl-[tubulin] + L-glutamate (RHEA:63796)

UniProt features (78 total): strand 28, helix 16, sequence variant 8, compositionally biased region 5, splice variant 4, sequence conflict 4, binding site 3, region of interest 3, turn 3, chain 1, domain 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
8V3M	X-RAY DIFFRACTION	1.8
8V3N	X-RAY DIFFRACTION	2.3
8V3O	X-RAY DIFFRACTION	2.3
8V3P	X-RAY DIFFRACTION	2.36
8V4L	ELECTRON MICROSCOPY	2.9
8V4M	ELECTRON MICROSCOPY	3
8V3Q	ELECTRON MICROSCOPY	3.1
8V4K	ELECTRON MICROSCOPY	3.1
8V3R	ELECTRON MICROSCOPY	3.4
8V3S	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDL9-F1	71.36	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 516 (proton donor/acceptor)

Ligand- & substrate-binding residues (3): 252; 255; 434

Post-translational modifications (1): 841

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8955332	Carboxyterminal post-translational modifications of tubulin
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 225 (showing top): GGGACCA_MIR133A_MIR133B, MULLIGHAN_NPM1_SIGNATURE_3_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOMF_METALLOPEPTIDASE_ACTIVITY, GCANCTGNY_MYOD_Q6, CMYB_01, SP3_Q3, MITSIADES_RESPONSE_TO_APLIDIN_DN, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, SP1_Q2_01, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, TGANTCA_AP1_C, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PEPTIDYL_GLUTAMIC_ACID_MODIFICATION

GO Biological Process (6): proteolysis (GO:0006508), protein deglutamylation (GO:0035608), C-terminal protein deglutamylation (GO:0035609), protein side chain deglutamylation (GO:0035610), protein branching point deglutamylation (GO:0035611), defense response to virus (GO:0051607)

GO Molecular Function (8): metallocarboxypeptidase activity (GO:0004181), zinc ion binding (GO:0008270), tubulin binding (GO:0015631), carboxypeptidase activity (GO:0004180), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), midbody (GO:0030496), mitotic spindle (GO:0072686), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein deglutamylation	3
cellular anatomical structure	3
intracellular membraneless organelle	2
protein metabolic process	1
peptidyl-glutamic acid modification	1
C-terminal protein amino acid modification	1
defense response	1
response to virus	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
transition metal ion binding	1
cytoskeletal protein binding	1
exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cytoskeleton	1
spindle	1
microtubule cytoskeleton	1

Protein interactions and networks

STRING

660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGBL5	TTLL6	Q8N841	702
AGBL5	TTLL4	Q14679	684
AGBL5	CGAS	Q8N884	626
AGBL5	TTL	Q8NG68	575
AGBL5	TTLL5	Q6EMB2	568
AGBL5	TTLL10	Q6ZVT0	544
AGBL5	AGBL4	Q5VU57	519
AGBL5	TTLL1	O95922	506
AGBL5	SPATA46	Q5T0L3	498
AGBL5	CLP1	Q92989	477
AGBL5	TTLL11	Q8NHH1	474
AGBL5	OSBPL6	Q9BZF3	437
AGBL5	EVA1A	Q9H8M9	436
AGBL5	CCPG1	Q9ULG6	435
AGBL5	TTLL7	Q6ZT98	431

IntAct

19 interactions, top by confidence:

A	B	Type	Score
RYBP	CSNK2A2	psi-mi:“MI:0914”(association)	0.900
RELL2	OXSR1	psi-mi:“MI:0914”(association)	0.830
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
TPCN2	AP3B1	psi-mi:“MI:0914”(association)	0.530
GFOD1	PER1	psi-mi:“MI:0914”(association)	0.530
AGBL5	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
AGBL5	E6	psi-mi:“MI:0915”(physical association)	0.370
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
DNAJA2	DENND11	psi-mi:“MI:0914”(association)	0.350
EFNB1	KRBA1	psi-mi:“MI:0914”(association)	0.350
BTNL9	GPR89A	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
CAMK2A	SMCHD1	psi-mi:“MI:0914”(association)	0.350
PRPS2	SMCHD1	psi-mi:“MI:0914”(association)	0.350
AGBL5	HSPA8	psi-mi:“MI:0914”(association)	0.350
CAMK2A	MAP3K7	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): AGBL5 (Affinity Capture-MS), AGBL5 (Affinity Capture-MS), AGBL5 (Affinity Capture-MS), AGBL5 (Affinity Capture-MS), AGBL5 (Affinity Capture-MS), AGBL5 (Affinity Capture-MS), AGBL5 (Affinity Capture-RNA), TUBG1 (Co-localization), AGBL5 (Affinity Capture-MS), AGBL5 (Affinity Capture-MS), PCGF3 (Affinity Capture-MS), PCGF5 (Affinity Capture-MS), AGBL5 (Affinity Capture-RNA), AGBL5 (Affinity Capture-MS), AGBL5 (Affinity Capture-MS)

ESM2 similar proteins: A1YVX4, A3KMI0, A4IHD2, A6H8H2, A6H8T7, B0JZV4, B2GV17, B2RRD7, B8ARK7, D2GXM8, E1B9D8, G5E8P1, O76373, O95696, P32019, P41229, P41230, P55201, P97564, Q09M02, Q0P4M4, Q30DN6, Q38JA7, Q4R632, Q58CX9, Q58DC8, Q5RBG4, Q5U5Z8, Q5VZ89, Q5XUN4, Q62240, Q68EI3, Q6IQX0, Q6P158, Q6P5D3, Q7XWV4, Q7Z401, Q80Y84, Q8CDK2, Q8CDP0

Diamond homologs: A6H8T7, A9JRL3, B2GV17, D2GXM8, E1B9D8, E1C3P4, O76373, Q09296, Q09LZ8, Q09M02, Q09M05, Q0P4M4, Q4R632, Q4U2V3, Q5U5Z8, Q5VU57, Q641K1, Q6DD21, Q8CDK2, Q8CDP0, Q8I2A6, Q8NDL9, Q8NEM8, Q96MI9, Q9UPW5, Q9VY99, Q58CX9, B0JZV4, Q68EI3, P30795, A0A096LPI5, Q8N976, Q96MD7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	16
Uncertain significance	408
Likely benign	257
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070126	NM_021831.6(AGBL5):c.1250_1251del (p.Pro417fs)	Pathogenic
1076597	NM_021831.6(AGBL5):c.175C>T (p.Arg59Ter)	Pathogenic
1076684	NM_021831.6(AGBL5):c.508C>T (p.Gln170Ter)	Pathogenic
1176089	NM_021831.6(AGBL5):c.356G>A (p.Trp119Ter)	Pathogenic
1380079	NM_021831.6(AGBL5):c.791_794del (p.Gly264fs)	Pathogenic
1391360	NM_021831.6(AGBL5):c.143dup (p.Ser49fs)	Pathogenic
1453937	NM_021831.6(AGBL5):c.686dup (p.Pro229_Asp230insTer)	Pathogenic
1454291	NM_021831.6(AGBL5):c.1729C>T (p.Arg577Ter)	Pathogenic
1943801	NM_021831.6(AGBL5):c.1678C>T (p.Arg560Ter)	Pathogenic
2007082	NM_021831.6(AGBL5):c.1281dup (p.Ala428fs)	Pathogenic
2010574	NM_021831.6(AGBL5):c.1622dup (p.Pro542fs)	Pathogenic
2060317	NM_021831.6(AGBL5):c.1455T>G (p.Tyr485Ter)	Pathogenic
2061231	NM_021831.6(AGBL5):c.421dup (p.His141fs)	Pathogenic
2101909	NM_021831.6(AGBL5):c.1650C>G (p.Tyr550Ter)	Pathogenic
2129388	NM_021831.6(AGBL5):c.1209G>A (p.Trp403Ter)	Pathogenic
242932	NM_021831.6(AGBL5):c.883G>A (p.Asp295Asn)	Pathogenic
2784135	NM_021831.6(AGBL5):c.1950dup (p.Ser651Ter)	Pathogenic
2824954	NM_021831.6(AGBL5):c.1874dup (p.Asn625fs)	Pathogenic
2869501	NM_021831.6(AGBL5):c.658C>T (p.Arg220Ter)	Pathogenic
3027085	NM_021831.6(AGBL5):c.1801C>T (p.Arg601Ter)	Pathogenic
3248690	NM_021831.6(AGBL5):c.1775G>A (p.Trp592Ter)	Pathogenic
3720305	NM_021831.6(AGBL5):c.1459C>T (p.Arg487Ter)	Pathogenic
4764192	NM_021831.6(AGBL5):c.737_740dup (p.Leu247fs)	Pathogenic
812217	NM_021831.6(AGBL5):c.1787_1788del (p.His596fs)	Pathogenic
953450	NM_021831.6(AGBL5):c.603_606del (p.Gly202fs)	Pathogenic
960289	NM_021831.6(AGBL5):c.1634_1646dup (p.Arg549fs)	Pathogenic
1176088	NM_021831.6(AGBL5):c.163A>T (p.Asn55Tyr)	Likely pathogenic
1184585	NM_021831.6(AGBL5):c.323C>G (p.Pro108Arg)	Likely pathogenic
1493450	NM_021831.6(AGBL5):c.2242+2T>G	Likely pathogenic
1710121	NM_021831.6(AGBL5):c.1465del (p.Arg489fs)	Likely pathogenic

SpliceAI

2368 predictions. Top by Δscore:

Variant	Effect	Δscore
2:27053392:T:TA	acceptor_gain	1.0000
2:27053393:G:A	acceptor_gain	1.0000
2:27053400:A:AG	acceptor_gain	1.0000
2:27053400:AG:A	acceptor_gain	1.0000
2:27053400:AGGT:A	acceptor_loss	1.0000
2:27053401:G:GA	acceptor_gain	1.0000
2:27053401:GG:G	acceptor_gain	1.0000
2:27053401:GGT:G	acceptor_gain	1.0000
2:27053401:GGTC:G	acceptor_gain	1.0000
2:27053401:GGTCA:G	acceptor_gain	1.0000
2:27053569:TTGAG:T	donor_gain	1.0000
2:27053570:TGAG:T	donor_gain	1.0000
2:27053571:GAG:G	donor_gain	1.0000
2:27053571:GAGG:G	donor_gain	1.0000
2:27053572:AG:A	donor_gain	1.0000
2:27053572:AGG:A	donor_loss	1.0000
2:27053573:GG:G	donor_gain	1.0000
2:27053573:GGT:G	donor_loss	1.0000
2:27053574:G:GG	donor_gain	1.0000
2:27053574:GTA:G	donor_loss	1.0000
2:27054625:TGTA:T	acceptor_loss	1.0000
2:27054627:TAGC:T	acceptor_loss	1.0000
2:27054628:A:AG	acceptor_gain	1.0000
2:27054629:G:GA	acceptor_gain	1.0000
2:27054629:GC:G	acceptor_gain	1.0000
2:27054629:GCC:G	acceptor_gain	1.0000
2:27054629:GCCC:G	acceptor_gain	1.0000
2:27054629:GCCCC:G	acceptor_gain	1.0000
2:27054804:GAGG:G	donor_gain	1.0000
2:27054806:GG:G	donor_gain	1.0000

AlphaMissense

5770 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:27052987:T:C	F10S	1.000
2:27053139:G:C	D61H	1.000
2:27053144:T:G	C62W	1.000
2:27053173:G:T	R72M	1.000
2:27053406:T:A	W74R	1.000
2:27053406:T:C	W74R	1.000
2:27053422:T:A	V79D	1.000
2:27053490:T:G	Y102D	1.000
2:27053509:C:A	P108H	1.000
2:27053541:T:A	W119R	1.000
2:27053541:T:C	W119R	1.000
2:27054698:T:C	L207P	1.000
2:27055087:A:C	S248R	1.000
2:27055089:C:A	S248R	1.000
2:27055089:C:G	S248R	1.000
2:27055099:C:G	H252D	1.000
2:27055100:A:G	H252R	1.000
2:27055105:G:T	G254W	1.000
2:27055109:A:T	E255V	1.000
2:27055120:A:C	S259R	1.000
2:27055122:C:A	S259R	1.000
2:27055122:C:G	S259R	1.000
2:27055127:T:A	V261D	1.000
2:27055224:C:A	N293K	1.000
2:27055224:C:G	N293K	1.000
2:27055231:G:C	G296R	1.000
2:27055232:G:A	G296D	1.000
2:27055243:G:A	G300R	1.000
2:27055243:G:C	G300R	1.000
2:27055244:G:A	G300E	1.000

dbSNP variants (sampled 300 via entrez): RS1000154584 (2:27060698 T>C), RS1000202927 (2:27054851 G>A), RS1000209620 (2:27060696 G>C), RS1000373816 (2:27054186 G>A,T), RS1000397623 (2:27050479 G>A,C), RS1000428857 (2:27050197 C>A), RS1000541946 (2:27059240 T>A,G), RS1000648104 (2:27052297 C>T), RS1000724026 (2:27053783 G>A,T), RS1000763457 (2:27048783 A>G), RS1000791296 (2:27070469 A>G), RS1000822366 (2:27070677 G>C), RS1001061512 (2:27064926 T>A), RS1001110825 (2:27052541 G>T), RS1001155224 (2:27070943 A>C,G)

Disease associations

OMIM: gene MIM:615900 | disease phenotypes: MIM:617023, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 75	Strong	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
inherited retinal dystrophy	Definitive	AR

Mondo (3): retinitis pigmentosa 75 (MONDO:0014871), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa (MONDO:0019200)

Orphanet (2): Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0000980	Pallor
HP:0001105	Retinal atrophy
HP:0003621	Juvenile onset
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract
HP:0007843	Attenuation of retinal blood vessels
HP:0007994	Peripheral visual field loss
HP:0008046	Abnormal retinal vascular morphology

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST010697_14	Cortical surface area (min-P)	2.000000e-09
GCST010698_75	Subcortical volume (min-P)	2.000000e-13
GCST010699_41	Brain morphology (min-P)	2.000000e-08
GCST010700_38	Cortical thickness (MOSTest)	3.000000e-08
GCST010701_56	Cortical surface area (MOSTest)	4.000000e-16
GCST010702_20	Subcortical volume (MOSTest)	2.000000e-64
GCST010703_76	Brain morphology (MOSTest)	1.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
sodium arsenite	decreases expression, increases abundance	2
Acetaminophen	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression, increases methylation	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects expression	1
butyraldehyde	decreases expression	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
entinostat	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Phthalic Acids	increases methylation	1
Silicon Dioxide	decreases methylation	1

Clinical trials (associated diseases)

259 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)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
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