POC1B

Summary

POC1B (POC1 centriolar protein B, HGNC:30836) is a protein-coding gene on chromosome 12q21.33, encoding POC1 centriolar protein homolog B (Q8TC44). Plays an important role in centriole assembly and/or stability and ciliogenesis.

POC1 proteins contain an N-terminal WD40 domain and a C-terminal coiled coil domain and are part of centrosomes. They play an important role in basal body and cilia formation. This gene encodes one of the two POC1 proteins found in humans. Mutation in this gene result in autosomal-recessive cone-rod dystrophy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 282809 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cone-rod dystrophy 20 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 25
• Clinical variants (ClinVar): 376 total — 30 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 23
• MANE Select transcript: NM_172240

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30836
Approved symbol	POC1B
Name	POC1 centriolar protein B
Location	12q21.33
Locus type	gene with protein product
Status	Approved
Aliases	TUWD12, FLJ14923
Ensembl gene	ENSG00000139323
Ensembl biotype	protein_coding
OMIM	614784
Entrez	282809

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 12 protein_coding, 5 nonsense_mediated_decay, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000313546, ENST00000393179, ENST00000539190, ENST00000546740, ENST00000546830, ENST00000547274, ENST00000547496, ENST00000548715, ENST00000549035, ENST00000549304, ENST00000549504, ENST00000549591, ENST00000551819, ENST00000552563, ENST00000850975, ENST00000867691, ENST00000867692, ENST00000867693, ENST00000867694, ENST00000867695, ENST00000867696, ENST00000928752, ENST00000928753, ENST00000928754

RefSeq mRNA: 5 — MANE Select: NM_172240 NM_001199777, NM_001425771, NM_001425772, NM_001425773, NM_172240

CCDS: CCDS31869, CCDS55859

Canonical transcript exons

ENST00000313546 — 12 exons

Exon	Start	End
ENSE00002348328	89525881	89526047
ENSE00003499246	89459638	89459718
ENSE00003512779	89470361	89470494
ENSE00003579505	89472168	89472275
ENSE00003586836	89419718	89421257
ENSE00003593499	89467617	89467685
ENSE00003603671	89497171	89497342
ENSE00003647319	89425161	89425379
ENSE00003657685	89466770	89466922
ENSE00003664596	89491936	89492115
ENSE00003674491	89525120	89525204
ENSE00003680916	89471614	89471729

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 96.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.7195 / max 27.0510, expressed in 1037 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132461	6.0931	1675
132456	0.6268	366
132457	0.5894	324
132458	0.5032	265
132462	0.0349	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	96.86	silver quality
sperm	CL:0000019	93.80	gold quality
corpus callosum	UBERON:0002336	92.62	gold quality
secondary oocyte	CL:0000655	92.52	gold quality
oocyte	CL:0000023	90.68	gold quality
epithelium of nasopharynx	UBERON:0001951	90.52	gold quality
endometrium	UBERON:0001295	90.51	gold quality
nasopharynx	UBERON:0001728	90.50	gold quality
pancreatic ductal cell	CL:0002079	89.86	gold quality
calcaneal tendon	UBERON:0003701	88.94	gold quality
colonic epithelium	UBERON:0000397	88.65	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.47	gold quality
bone marrow cell	CL:0002092	88.05	gold quality
monocyte	CL:0000576	88.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.95	gold quality
leukocyte	CL:0000738	87.81	gold quality
spinal cord	UBERON:0002240	87.66	gold quality
ileal mucosa	UBERON:0000331	87.07	gold quality
amniotic fluid	UBERON:0000173	86.93	gold quality
rectum	UBERON:0001052	86.83	gold quality
palpebral conjunctiva	UBERON:0001812	86.55	gold quality
blood	UBERON:0000178	86.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.21	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.03	gold quality
subthalamic nucleus	UBERON:0001906	84.97	gold quality
bone marrow	UBERON:0002371	84.88	gold quality
tonsil	UBERON:0002372	84.72	gold quality
gingival epithelium	UBERON:0001949	84.71	gold quality
colonic mucosa	UBERON:0000317	84.66	gold quality
uterus	UBERON:0000995	84.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7249	no	206.48
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting POC1B, 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-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-579-3P	99.86	71.66	3628

Literature-anchored findings (GeneRIF, showing 19)

• Based on these data, we propose that Pix1 and Pix2 are microtubule-associated adaptor proteins that likely contribute to a range of developmental and cell division processes. (PMID:18068700)
• Poc1B is required for primary ciliogenesis; Poc1 provides a molecular link between the assembly and stability of centrioles for ciliary-based motility in T. thermophila and cilia formation and function in zebrafish and humans (PMID:20008567)
• Poc1A and Poc1B play redundant, but essential, roles in generation of stable centrioles, but Poc1B may have additional independent functions during cell cycle progression. (PMID:23015594)
• POC1B is a novel gene for a new disease typical of cone-rod dystrophy except that patients did not report night blindness. (PMID:24945461)
• POC1B mutations result in a defect of the photoreceptor sensory cilium and thus affect cone and rod photoreceptors. (PMID:25018096)
• Study indicates that POC1B is required for retinal integrity, and is proposed POC1B mutations as a probable cause for Joubert syndrome with severe polycystic kidney disease. (PMID:25044745)
• Study found that homozygous POC1B mutation, i.e., c.737C –> T(p.T246 M), cosegregated with the phenotype of a tested family, indicating that POC1B gene was the most possible pathogenic gene for paroxysmal kinesigenic dyskinesia (PMID:26650803)
• Intronic SNP in POC1B/GALNT4 locus (rs11105306) was associated with NT-proBNP levels in patients with acute coronary syndrome (ACS). The POC1B/GALNT4 SNP was not associated with higher risk of cardiovascular death. (PMID:26908625)
• Depletion of CEP295 blocks the incorporation of POC5 and POC1B into the distal portion of centrioles and suppresses the post-translational modification of centriolar microtubules . Our study thus uncovers a new role for CEP295 during centriole elongation. (PMID:27185865)
• The cone dystrophy associated with POC1B variants has features similar to achromatopsia, and genetic analyses is useful in discriminating these two diseases. (PMID:29220607)
• Compound heterozygous mutation in the POC1B gene is associated with peripheral cone dystrophy. (PMID:29377742)
• Generalized or peripheral cone dystrophy with normal funduscopic appearance is the representative phenotype of POC1B-associated retinopathy in our cohort. (PMID:31390656)
• Increasing the Genetic Diagnosis Yield in Inherited Retinal Dystrophies: Assigning Pathogenicity to Novel Non-canonical Splice Site Variants. (PMID:32244552)
• A homozygous POC1B variant causes recessive cone-rod dystrophy. (PMID:33657974)
• Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants. (PMID:34065499)
• Differential Expression Study of Lysine Crotonylation and Proteome for Chronic Obstructive Pulmonary Disease Combined with Type II Respiratory Failure. (PMID:34221209)
• Seroreactivity against retinal proteins in a case of POC1B gene associated cone dystrophy with normal funduscopic appearance: a systematic approach to diagnosis. (PMID:36094084)
• Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice. (PMID:37070736)
• Phenotypic and genotypic features of POC1B-associated cone dystrophy. (PMID:37246743)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Poc1b	ENSMUSG00000019952
rattus_norvegicus	Poc1b	ENSRNOG00000024450

Paralogs (26): PAFAH1B1 (ENSG00000007168), SNRNP40 (ENSG00000060688), WDR62 (ENSG00000075702), WDR7 (ENSG00000091157), TBL2 (ENSG00000106638), PAK1IP1 (ENSG00000111845), WDR75 (ENSG00000115368), DCAF4 (ENSG00000119599), DAW1 (ENSG00000123977), TEP1 (ENSG00000129566), AHI1 (ENSG00000135541), WDR38 (ENSG00000136918), MAPKBP1 (ENSG00000137802), NEDD1 (ENSG00000139350), COP1 (ENSG00000143207), WDR17 (ENSG00000150627), WDR43 (ENSG00000163811), POC1A (ENSG00000164087), WDR88 (ENSG00000166359), WDR81 (ENSG00000167716), DCAF4L2 (ENSG00000176566), DCAF4L1 (ENSG00000182308), WDR27 (ENSG00000184465), NWD1 (ENSG00000188039), WDR5 (ENSG00000196363), WDR5B (ENSG00000196981)

Protein

Protein identifiers

POC1 centriolar protein homolog B — Q8TC44 (reviewed: Q8TC44)

Alternative names: Pix1, Proteome of centriole protein 1B, WD repeat-containing protein 51B

All UniProt accessions (5): Q8TC44, A0MNP0, F8VV91, F8VX21, Q8IU52

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in centriole assembly and/or stability and ciliogenesis. Involved in early steps of centriole duplication, as well as in the later steps of centriole length control. Acts in concert with POC1A to ensure centriole integrity and proper mitotic spindle formation. Required for primary cilia formation, ciliary length and also cell proliferation. Required for retinal integrity. Acts as a positive regulator of centriole elongation.

Subunit / interactions. Interacts with POC1A. Interacts with FAM161A. Interacts with CEP44; the interaction is direct and recruits POC1B to centriolar microtubules. Forms a microtubule-associated complex with POC5, CETN2 and FAM161A. Interacts with CCDC15.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Cilium basal body. Spindle pole.

Tissue specificity. Expressed in the retina.

Post-translational modifications. Phosphorylated in mitotic cells that may be mediated by CDK1.

Disease relevance. Cone-rod dystrophy 20 (CORD20) [MIM:615973] A form of cone-rod dystrophy, an inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the WD repeat POC1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TC44-1	1	yes
Q8TC44-2	2

RefSeq proteins (5): NP_001186706, NP_001412700, NP_001412701, NP_001412702, NP_758440* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR050505	WDR55/POC1	Family

Pfam: PF00400

UniProt features (13 total): repeat 7, sequence variant 2, chain 1, splice variant 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TC44-F1	77.62	0.55

Functional residue map

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

Post-translational modifications (1): 321

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 230 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_VESICLE_ORGANIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_REGULATION_OF_CENTRIOLE_REPLICATION, GOBP_CENTRIOLE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, chr12q21, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT

GO Biological Process (14): cell morphogenesis (GO:0000902), acrosome assembly (GO:0001675), retina homeostasis (GO:0001895), centriole replication (GO:0007099), single fertilization (GO:0007338), cell population proliferation (GO:0008283), homeostasis of number of cells (GO:0048872), cilium assembly (GO:0060271), sperm flagellum assembly (GO:0120316), positive regulation of centriole elongation (GO:1903724), microtubule-based process (GO:0007017), spermatogenesis (GO:0007283), cell projection organization (GO:0030030), multicellular organismal-level homeostasis (GO:0048871)

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

GO Cellular Component (7): spindle pole (GO:0000922), centrosome (GO:0005813), centriole (GO:0005814), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	3
cellular anatomical structure	3
microtubule organizing center	3
spermatid development	2
organelle assembly	2
cellular process	2
intracellular membraneless organelle	2
anatomical structure morphogenesis	1
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
tissue homeostasis	1
cell cycle process	1
centrosome duplication	1
centriole assembly	1
fertilization	1
multicellular organismal-level homeostasis	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
flagellated sperm motility	1
motile cilium assembly	1
positive regulation of centriole replication	1
centriole elongation	1
regulation of centriole elongation	1
male gamete generation	1
cellular component organization	1
multicellular organismal process	1
homeostatic process	1
binding	1
spindle	1
centriole	1
cilium	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1954 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POC1B	POC5	Q8NA72	961
POC1B	FAM161A	Q3B820	935
POC1B	CETN2	P41208	781
POC1B	CEP295	Q9C0D2	719
POC1B	WDR90	Q96KV7	718
POC1B	SASS6	Q6UVJ0	672
POC1B	CEP135	Q66GS9	671
POC1B	CFAP418	Q96NL8	666
POC1B	CEP120	Q8N960	648
POC1B	RTTN	Q86VV8	624
POC1B	RPGRIP1	Q96KN7	616
POC1B	RPGR	Q92834	600
POC1B	PLK4	O00444	573
POC1B	SPICE1	Q8N0Z3	571
POC1B	CNTROB	Q8N137	553

IntAct

40 interactions, top by confidence:

A	B	Type	Score
SIL1	HSPA5	psi-mi:“MI:0914”(association)	0.740
CUL4B	CUL4A	psi-mi:“MI:0914”(association)	0.730
POC1B	NUDC	psi-mi:“MI:0915”(physical association)	0.730
TDP1	XRCC1	psi-mi:“MI:0914”(association)	0.670
AKIP1	POC1A	psi-mi:“MI:0914”(association)	0.610
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
COG6	EXOC5	psi-mi:“MI:0914”(association)	0.530
CORO1A	VARS1	psi-mi:“MI:0914”(association)	0.530
POC1A	TXNDC9	psi-mi:“MI:0914”(association)	0.480
Poc1b		psi-mi:“MI:0915”(physical association)	0.400
Cep44	SSR3	psi-mi:“MI:0914”(association)	0.350
	ATP6	psi-mi:“MI:0914”(association)	0.350
POC1A	POTEF	psi-mi:“MI:0914”(association)	0.350
POC1B	TACC1	psi-mi:“MI:0914”(association)	0.350
NELL2	MATN2	psi-mi:“MI:0914”(association)	0.350
KDM4A	PIPSL	psi-mi:“MI:0914”(association)	0.350
KMT5C	CBX4	psi-mi:“MI:0914”(association)	0.350
TDRD3	PTMA	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
INSYN1	CCDC85C	psi-mi:“MI:0914”(association)	0.350
CORO1A	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
SIL1	NME2P1	psi-mi:“MI:0914”(association)	0.350
MIIP	NMT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (551): FAM161A (Two-hybrid), POC1B (Affinity Capture-Western), FAM161A (Affinity Capture-Western), POC1B (Affinity Capture-MS), POC1B (Affinity Capture-MS), POC1B (Proximity Label-MS), POC1B (Proximity Label-MS), BAG2 (Proximity Label-MS), CAD (Proximity Label-MS), CCT2 (Proximity Label-MS), CDC37 (Proximity Label-MS), CEP44 (Proximity Label-MS), CLTC (Proximity Label-MS), KIAA1524 (Proximity Label-MS), MIIP (Proximity Label-MS)

ESM2 similar proteins: A0JP70, A2CEH0, B0X2V9, B3MET8, B3NSK1, B4GIJ0, B4HND9, B4J8H6, B4KRQ4, B4MFM2, B4P7H8, B4QB64, D3ZW91, F6ZT52, O00423, O61585, Q05B17, Q05BC3, Q16MY0, Q1LZ08, Q28I85, Q28YY2, Q2TBP4, Q32PG3, Q4R2Z6, Q4V7Y7, Q4V7Z1, Q4V8C3, Q5F3K4, Q5RAW8, Q5RD06, Q5ZIU8, Q5ZLG9, Q6NVM2, Q6PFM9, Q6PJI9, Q6S7B0, Q7T0P4, Q7ZUV2, Q7ZVF0

Diamond homologs: A2CEH0, D3ZW91, F6ZT52, Q229Z6, Q28I85, Q2TBP4, Q4V7Z1, Q5RD06, Q6NWV3, Q6NYH1, Q7T0P4, Q7ZVF0, Q8BHD1, Q8JZX3, Q8NBT0, Q8TC44, Q9VU65, B6QC06, Q9FLX9, Q9HBG6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	9
Uncertain significance	170
Likely benign	116
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1029264	NM_172240.3(POC1B):c.144del (p.Lys48fs)	Pathogenic
1070499	NM_172240.3(POC1B):c.247del (p.Thr83fs)	Pathogenic
1323482	NM_172240.3(POC1B):c.417del (p.Leu140fs)	Pathogenic
1397795	NM_172240.3(POC1B):c.1079_1080del (p.Pro360fs)	Pathogenic
1408249	NM_172240.3(POC1B):c.1312C>T (p.Gln438Ter)	Pathogenic
1430739	NC_000012.11:g.(?89853395)(89866072_?)del	Pathogenic
1442201	NM_172240.3(POC1B):c.575del (p.Val192fs)	Pathogenic
1452972	NM_172240.3(POC1B):c.316C>T (p.Arg106Ter)	Pathogenic
1453037	NM_172240.3(POC1B):c.513G>A (p.Trp171Ter)	Pathogenic
1455684	NM_172240.3(POC1B):c.1061del (p.Leu354fs)	Pathogenic
1456760	NM_172240.3(POC1B):c.887T>G (p.Leu296Ter)	Pathogenic
1457070	NM_172240.3(POC1B):c.678del (p.His227fs)	Pathogenic
1468791	NM_172240.3(POC1B):c.1295T>A (p.Leu432Ter)	Pathogenic
155769	NM_172240.3(POC1B):c.317G>C (p.Arg106Pro)	Pathogenic
155770	NM_172240.3(POC1B):c.199_201del (p.Gln67del)	Pathogenic
155771	NM_172240.3(POC1B):c.810+1G>T	Pathogenic
1915007	NM_172240.3(POC1B):c.1083dup (p.Met362fs)	Pathogenic
1963710	NM_172240.3(POC1B):c.607dup (p.Ser203fs)	Pathogenic
1965299	NM_172240.3(POC1B):c.703_704del (p.Ser235fs)	Pathogenic
1967719	NM_172240.3(POC1B):c.810+2T>G	Pathogenic
2089306	NM_172240.3(POC1B):c.1231_1232del (p.Glu411fs)	Pathogenic
2419007	NM_172240.3(POC1B):c.356C>T (p.Thr119Ile)	Pathogenic
2796810	NM_172240.3(POC1B):c.260G>A (p.Trp87Ter)	Pathogenic
3248851	NM_172240.3(POC1B):c.879+2T>G	Pathogenic
3611083	NM_172240.3(POC1B):c.934del (p.Arg312fs)	Pathogenic
3611635	NM_172240.3(POC1B):c.959del (p.Asp320fs)	Pathogenic
3685609	NM_172240.3(POC1B):c.16G>T (p.Glu6Ter)	Pathogenic
4075856	GRCh37/hg19 12q21.33(chr12:89841834-89872628)x1	Pathogenic
4279467	GRCh37/hg19 12q21.33(chr12:89841834-89873796)x1	Pathogenic
4728803	NM_172240.3(POC1B):c.877_878del (p.Gln293fs)	Pathogenic

SpliceAI

2744 predictions. Top by Δscore:

Variant	Effect	Δscore
12:89459636:A:AC	donor_gain	1.0000
12:89459637:C:CC	donor_gain	1.0000
12:89460050:A:T	acceptor_gain	1.0000
12:89466762:ATACT:A	donor_loss	1.0000
12:89466764:ACTC:A	donor_loss	1.0000
12:89466765:CTCA:C	donor_gain	1.0000
12:89466766:TCA:T	donor_loss	1.0000
12:89466767:CAC:C	donor_loss	1.0000
12:89466768:A:AC	donor_gain	1.0000
12:89466768:ACTT:A	donor_gain	1.0000
12:89466769:C:CT	donor_gain	1.0000
12:89466769:CT:C	donor_gain	1.0000
12:89466769:CTT:C	donor_gain	1.0000
12:89466769:CTTC:C	donor_gain	1.0000
12:89466769:CTTCT:C	donor_gain	1.0000
12:89466922:CCT:C	acceptor_loss	1.0000
12:89466923:C:A	acceptor_loss	1.0000
12:89466923:C:CC	acceptor_gain	1.0000
12:89470364:ATGT:A	donor_gain	1.0000
12:89470367:T:TA	donor_gain	1.0000
12:89470391:T:TA	donor_gain	1.0000
12:89470492:GAAC:G	acceptor_loss	1.0000
12:89470493:AAC:A	acceptor_loss	1.0000
12:89470494:AC:A	acceptor_loss	1.0000
12:89470495:C:CC	acceptor_gain	1.0000
12:89470496:T:G	acceptor_loss	1.0000
12:89470500:T:C	acceptor_gain	1.0000
12:89470500:T:TC	acceptor_gain	1.0000
12:89470502:G:GC	acceptor_gain	1.0000
12:89472162:ACTT:A	donor_loss	1.0000

AlphaMissense

3126 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:89470437:G:T	T245K	0.999
12:89472217:A:G	W171R	0.999
12:89472217:A:T	W171R	0.999
12:89472235:C:G	D165H	0.999
12:89472239:A:C	S163R	0.999
12:89472239:A:T	S163R	0.999
12:89472241:T:G	S163R	0.999
12:89472247:A:G	S161P	0.999
12:89492003:A:G	W129R	0.999
12:89492003:A:T	W129R	0.999
12:89492020:T:A	D123V	0.999
12:89492020:T:G	D123A	0.999
12:89492021:C:G	D123H	0.999
12:89492026:G:A	S121F	0.999
12:89492027:A:G	S121P	0.999
12:89492074:A:T	V105D	0.999
12:89421232:A:G	L453P	0.998
12:89425177:A:G	L439P	0.998
12:89470437:G:C	T245R	0.998
12:89472240:C:A	S163I	0.998
12:89492007:T:A	K127N	0.998
12:89492007:T:G	K127N	0.998
12:89492011:A:T	I126K	0.998
12:89492026:G:T	S121Y	0.998
12:89492029:G:T	A120D	0.998
12:89492032:G:C	T119R	0.998
12:89492032:G:T	T119K	0.998
12:89497184:A:G	W87R	0.998
12:89497184:A:T	W87R	0.998
12:89497202:C:G	D81H	0.998

dbSNP variants (sampled 300 via entrez): RS1000004410 (12:89490608 G>A), RS1000044283 (12:89445600 A>G), RS1000058676 (12:89441927 G>C), RS1000086264 (12:89441744 A>C,G), RS1000118267 (12:89490812 G>A), RS1000148793 (12:89441264 T>A,C), RS1000165935 (12:89462042 T>C,G), RS1000167118 (12:89493526 T>A), RS1000189941 (12:89516332 C>G), RS1000216019 (12:89462488 G>A), RS1000270411 (12:89439266 C>G), RS1000280165 (12:89423550 A>T), RS1000280913 (12:89470240 T>G), RS1000328625 (12:89499931 T>C), RS1000351881 (12:89423999 C>G,T)

Disease associations

OMIM: gene MIM:614784 | disease phenotypes: MIM:615973

GenCC curated gene-disease

Disease	Classification	Inheritance
cone-rod dystrophy 20	Definitive	Autosomal recessive
ciliopathy	Moderate	Autosomal recessive
cone-rod dystrophy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
cone-rod dystrophy 20	Definitive	AR

Mondo (4): cone-rod dystrophy 20 (MONDO:0014427), inherited retinal dystrophy (MONDO:0019118), ciliopathy (MONDO:0005308), cone-rod dystrophy (MONDO:0015993)

Orphanet (2): Cone rod dystrophy (Orphanet:1872), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

23 total (24 of 23 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000529	Progressive visual loss
HP:0000543	Optic disc pallor
HP:0000548	Cone/cone-rod dystrophy
HP:0000551	Color vision defect
HP:0000552	Tritanomaly
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0001105	Retinal atrophy
HP:0001133	Constriction of peripheral visual field
HP:0003593	Infantile onset
HP:0007641	Dyschromatopsia
HP:0007663	Reduced visual acuity
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007843	Attenuation of retinal blood vessels
HP:0011003	High myopia
HP:0011463	Childhood onset
HP:0012508	Metamorphopsia
HP:0030466	Abnormal full-field electroretinogram
HP:0000556	Retinal dystrophy

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST002497_20	Blood pressure	4.000000e-08
GCST002497_21	Blood pressure	2.000000e-07
GCST003298_3	NT-proBNP levels in acute coronary syndrome	1.000000e-16
GCST003542_154	Night sleep phenotypes	6.000000e-06
GCST004608_180	Granulocyte percentage of myeloid white cells	5.000000e-10
GCST004625_124	Monocyte count	7.000000e-11
GCST005208_3	B-type natriuretic peptide to N-terminal pro B-type natriuretic peptide ratio	7.000000e-23
GCST005208_4	B-type natriuretic peptide to N-terminal pro B-type natriuretic peptide ratio	4.000000e-07
GCST006166_31	Diastolic blood pressure x alcohol consumption interaction (2df test)	1.000000e-15
GCST006167_29	Mean arterial pressure x alcohol consumption interaction (2df test)	2.000000e-17
GCST006167_60	Mean arterial pressure x alcohol consumption interaction (2df test)	4.000000e-13
GCST006171_7	Pulse pressure x alcohol consumption (light vs heavy) interaction (2df test)	6.000000e-11
GCST006190_37	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	8.000000e-47
GCST006190_90	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-39
GCST006192_10	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-54
GCST006192_24	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-41
GCST006193_21	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-44
GCST006193_61	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-37
GCST006195_2	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-39
GCST006195_51	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-52
GCST006434_34	Systolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-16
GCST008310_11	Cardiac Troponin-T levels	1.000000e-07
GCST90002388_436	Lymphocyte count	1.000000e-10
GCST90002393_422	Monocyte count	8.000000e-16
GCST90002394_374	Monocyte percentage of white cells	3.000000e-09

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0006340	mean arterial pressure
EFO:0006335	systolic blood pressure
EFO:0005278	cardiovascular disease biomarker measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0005091	monocyte count
EFO:0008469	B-type natriuretic peptide to N-terminal pro B-type natriuretic peptide ratio
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006527	smoking status measurement
EFO:0005043	cardiac troponin T measurement
EFO:0004587	lymphocyte count
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
beta-lapachone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
torcetrapib	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Bortezomib	increases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Ethinyl Estradiol	affects expression	1
Methyl Methanesulfonate	increases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	decreases expression	1
Genistein	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
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]
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)
NCT00068224	Not specified	COMPLETED	Clinical and Molecular Investigations Into Ciliopathies
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT06467344	PHASE1/PHASE2	RECRUITING	Study to Evaluate ACDN-01 in ABCA4-related Stargardt Retinopathy (STELLAR)
NCT06789445	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO)
NCT00427180	Not specified	UNKNOWN	IRIS PILOT - Extended Pilot Study With a Retinal Implant System
NCT01864486	Not specified	COMPLETED	Restoring Vision With the Intelligent Retinal Implant System (IRIS V1)in Patients With Retinal Dystrophy
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02670980	Not specified	COMPLETED	Compensation for Blindness With the Intelligent Retinal Implant System (IRIS V2) in Patients With Retinal Dystrophy
NCT04658251	Not specified	TERMINATED	Study of New Mutations in Cone Disorders
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
NCT06445322	Not specified	RECRUITING	Prescreening Study to Identify Potential Stargardt Participants for ACDN-01 Clinical Trials (STARPATH)
NCT07548944	Not specified	RECRUITING	Observational Study to Investigate the Short-term Effects of Transcorneal Electrical Stimulation on Visual Performance
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography