RCBTB1

Summary

RCBTB1 (RCC1 and BTB domain containing protein 1, HGNC:18243) is a protein-coding gene on chromosome 13q14.2, encoding RCC1 and BTB domain-containing protein 1 (Q8NDN9). May be involved in cell cycle regulation by chromatin remodeling.

This gene encodes a protein with an N-terminal RCC1 domain and a C-terminal BTB (broad complex, tramtrack and bric-a-brac) domain. In rat, over-expression of this gene in vascular smooth muscle cells induced cellular hypertrophy. In rat, the C-terminus of RCBTB1 interacts with the angiotensin II receptor-1A. In humans, this gene maps to a region of chromosome 13q that is frequently deleted in B-cell chronic lymphocytic leukemia and other lymphoid malignancies.

Source: NCBI Gene 55213 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RCBTB1-related retinopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 457 total — 21 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 10
• MANE Select transcript: NM_018191

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18243
Approved symbol	RCBTB1
Name	RCC1 and BTB domain containing protein 1
Location	13q14.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10716, CLLD7, CLLL7
Ensembl gene	ENSG00000136144
Ensembl biotype	protein_coding
OMIM	607867
Entrez	55213

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 16 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000258646, ENST00000378302, ENST00000471984, ENST00000490058, ENST00000860932, ENST00000860933, ENST00000860934, ENST00000860935, ENST00000919057, ENST00000919058, ENST00000919059, ENST00000949631, ENST00000949632, ENST00000949633, ENST00000949634, ENST00000949635, ENST00000949636, ENST00000949637

RefSeq mRNA: 8 — MANE Select: NM_018191 NM_001352500, NM_001352501, NM_001352502, NM_001352503, NM_001352504, NM_001352505, NM_001352506, NM_018191

CCDS: CCDS9418

Canonical transcript exons

ENST00000378302 — 13 exons

Exon	Start	End
ENSE00000923478	49540876	49541006
ENSE00000923479	49541676	49541827
ENSE00000923480	49544737	49544863
ENSE00000923481	49549458	49549648
ENSE00000939637	49551326	49551468
ENSE00001004016	49559918	49560084
ENSE00001004021	49566618	49566768
ENSE00001004023	49552178	49552285
ENSE00001004024	49555515	49555673
ENSE00001390320	49531946	49534262
ENSE00001476994	49567154	49567320
ENSE00001476997	49585444	49585558
ENSE00001532255	49580505	49580584

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 94.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3140 / max 88.0971, expressed in 1750 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137321	7.1078	1704
137320	1.4539	694
137322	0.3852	187
137323	0.3671	203

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	94.69	gold quality
pigmented layer of retina	UBERON:0001782	94.07	gold quality
decidua	UBERON:0002450	93.94	gold quality
left lobe of thyroid gland	UBERON:0001120	93.46	gold quality
right lobe of thyroid gland	UBERON:0001119	93.45	gold quality
medial globus pallidus	UBERON:0002477	93.30	gold quality
thyroid gland	UBERON:0002046	92.93	gold quality
globus pallidus	UBERON:0001875	92.66	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.96	gold quality
mucosa of stomach	UBERON:0001199	91.83	gold quality
spinal cord	UBERON:0002240	91.68	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.32	gold quality
subthalamic nucleus	UBERON:0001906	91.26	gold quality
substantia nigra	UBERON:0002038	91.18	gold quality
substantia nigra pars compacta	UBERON:0001965	90.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.85	gold quality
midbrain	UBERON:0001891	90.83	gold quality
right adrenal gland cortex	UBERON:0035827	90.80	gold quality
inferior vagus X ganglion	UBERON:0005363	90.60	gold quality
right adrenal gland	UBERON:0001233	90.39	gold quality
secondary oocyte	CL:0000655	90.28	gold quality
corpus callosum	UBERON:0002336	90.08	gold quality
left adrenal gland	UBERON:0001234	90.05	gold quality
left adrenal gland cortex	UBERON:0035825	89.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.88	gold quality
nasal cavity mucosa	UBERON:0001826	89.75	gold quality
adrenal cortex	UBERON:0001235	89.64	gold quality
lateral globus pallidus	UBERON:0002476	89.64	gold quality
islet of Langerhans	UBERON:0000006	89.44	gold quality
cortical plate	UBERON:0005343	89.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	188.06
E-ANND-3	yes	4.83
E-CURD-10	no	138.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

108 targeting RCBTB1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
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-218-5P	99.93	72.22	2103
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3140-3P	99.88	68.47	2069

Literature-anchored findings (GeneRIF, showing 10)

• E4.5 gene, which maps at chromosome band 13q14.3, encodes for a 4 kb mRNA expressed in various tissues and has an open reading frame of 531 amino acids. It has a potential role in the pathogenesis of chronic lymphocytic leukemia [E4.5] (PMID:14565662)
• Data show that the biological actions of Clld7 are consistent with those of a tumor suppressor. (PMID:20926398)
• Study identifies RCBTB1 as a modifier of the smoking effect on carotid intima-media thickness. (PMID:24202307)
• Results identified RCBTB1 as a gene associated with vitreoretinopathy and found that it plays a role in retinal angiogenesis through Norrin-induced beta-catenin signaling. (PMID:26908610)
• Data indicate RNA Binding Protein with Multiple Splicing (RBPMS), Regulator of Chromosome Condensation and POZ Domain Containing Protein 1 (RCBTB1), and Zinc Finger protein 608 (ZNF608) as miR-21-3p target genes. (PMID:27166999)
• study puts forward mutations in RCBTB1 as a cause of autosomal-recessive non-syndromic and syndromic inherited retinal dystrophies; data support a role for impaired ubiquitination in the pathogenetic mechanism of RCBTB1 mutations (PMID:27486781)
• Variants in RCBTB1 are Associated with Autosomal Recessive Retinitis Pigmentosa but Not Autosomal Dominant FEVR. (PMID:33104391)
• Deep clinical phenotyping and gene expression analysis in a patient with RCBTB1-associated retinopathy. (PMID:33624564)
• Novel RCBTB1 variants causing later-onset non-syndromic retinal dystrophy with macular chorioretinal atrophy. (PMID:35057699)
• Expression of CLLD7 and CHC1L Proteins in Oral Epithelial Dysplasia in a Group of Thai Patients. (PMID:38679985)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rcbtb1	ENSDARG00000036645
mus_musculus	Rcbtb1	ENSMUSG00000035469
rattus_norvegicus	Rcbtb1	ENSRNOG00000021712
drosophila_melanogaster	ca	FBGN0000247
drosophila_melanogaster	Rcc1	FBGN0002638
drosophila_melanogaster	CG7420	FBGN0031344
caenorhabditis_elegans		WBGENE00004304

Paralogs (9): ALS2 (ENSG00000003393), HERC1 (ENSG00000103657), SERGEF (ENSG00000129158), RCBTB2 (ENSG00000136161), RPGR (ENSG00000156313), RCCD1 (ENSG00000166965), RCC2 (ENSG00000179051), RCC1 (ENSG00000180198), RCC1L (ENSG00000274523)

Protein

Protein identifiers

RCC1 and BTB domain-containing protein 1 — Q8NDN9 (reviewed: Q8NDN9)

Alternative names: Chronic lymphocytic leukemia deletion region gene 7 protein, Regulator of chromosome condensation and BTB domain-containing protein 1

All UniProt accessions (1): Q8NDN9

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in cell cycle regulation by chromatin remodeling.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed. In the retina, present in the nerve fiber layer and to a lesser extent in the inner and outer plexiform layers (at protein level).

Disease relevance. Retinal dystrophy with or without extraocular anomalies (RDEOA) [MIM:617175] An autosomal recessive disease characterized by progressive retinal dystrophy, chorioretinal macular atrophy, reduced cone and rod responses on ERG, and decrease visual acuity. Extraocular anomalies are variably present in some patients and include pulmonary fibrosis, sensorineural hearing loss, and endocrine features such as goiter and primary ovarian insufficiency. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NDN9-1	1	yes
Q8NDN9-2	2

RefSeq proteins (8): NP_001339429, NP_001339430, NP_001339431, NP_001339432, NP_001339433, NP_001339434, NP_001339435, NP_060661* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR000408	Reg_chr_condens	Repeat
IPR009091	RCC1/BLIP-II	Homologous_superfamily
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR047996	RCBTB1_BTB_POZ	Domain
IPR051625	Signaling_Regulatory_Domain	Family
IPR058923	RCC1-like_dom	Domain

Pfam: PF00651, PF25390

UniProt features (20 total): sequence variant 8, repeat 6, splice variant 2, domain 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDN9-F1	92.98	0.76

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): PAL_PRMT5_TARGETS_UP, GOZGIT_ESR1_TARGETS_DN, CHUANG_OXIDATIVE_STRESS_RESPONSE_UP, ONKEN_UVEAL_MELANOMA_UP, PU1_Q6, SAFFORD_T_LYMPHOCYTE_ANERGY, chr13q14, LAIHO_COLORECTAL_CANCER_SERRATED_DN, LINDGREN_BLADDER_CANCER_CLUSTER_1_DN, AAGCACA_MIR218, KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3, RAO_BOUND_BY_SALL4_ISOFORM_B, CAHOY_OLIGODENDROCUTIC, HOXA9_DN.V1_UP, TBK1.DF_DN

GO Biological Process (1): chromatin organization (GO:0006325)

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

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular component organization	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RCBTB1	PHF11	Q9UIL8	602
RCBTB1	ZNF408	Q9H9D4	599
RCBTB1	CDADC1	Q9BWV3	598
RCBTB1	CUL3	Q13618	576
RCBTB1	SETDB2	Q96T68	570
RCBTB1	OR6N1	Q8NGY5	570
RCBTB1	MLNR	O43193	534
RCBTB1	LITAFD	A0A1B0GVX0	518
RCBTB1	AGTR1	P30556	512
RCBTB1	SPRYD7	Q5W111	511
RCBTB1	CCDC106	Q9BWC9	507
RCBTB1	NUDT13	Q86X67	470
RCBTB1	TSPAN12	O95859	469
RCBTB1	OR6N2	Q8NGY6	463
RCBTB1	OR2C1	O95371	460

IntAct

37 interactions, top by confidence:

A	B	Type	Score
ABCD4	ABCD4	psi-mi:“MI:0914”(association)	0.640
PTGR3	DBT	psi-mi:“MI:0914”(association)	0.640
RCBTB1	ANKRD40	psi-mi:“MI:0915”(physical association)	0.560
RCBTB1	ANKRD40	psi-mi:“MI:0914”(association)	0.560
FOXR2	MYC	psi-mi:“MI:0914”(association)	0.530
S100A4	OIP5	psi-mi:“MI:0914”(association)	0.530
HSP90AB1	RCBTB1	psi-mi:“MI:0915”(physical association)	0.400
NUDCD1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
NUDCD1	DNAJB2	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CUL5	DDX3X	psi-mi:“MI:0914”(association)	0.350
RCBTB2	FECH	psi-mi:“MI:0914”(association)	0.350
rep	PCNT	psi-mi:“MI:0914”(association)	0.350
MAP1LC3A		psi-mi:“MI:0914”(association)	0.350
MAP1LC3B		psi-mi:“MI:0914”(association)	0.350
GABARAPL2		psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
GABARAP		psi-mi:“MI:0914”(association)	0.350
RAF1	EIF3CL	psi-mi:“MI:0914”(association)	0.350
RAF1	EIF3F	psi-mi:“MI:0914”(association)	0.350
RAF1	ARID1A	psi-mi:“MI:0914”(association)	0.350
RAF1	PRPF3	psi-mi:“MI:0914”(association)	0.350
S100A4	VWA8	psi-mi:“MI:0914”(association)	0.350
CD80	RIMOC1	psi-mi:“MI:0914”(association)	0.350
HOXB6	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
KIAA1191	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): ANKRD40 (Affinity Capture-MS), HERC3 (Affinity Capture-MS), HELZ (Affinity Capture-MS), RCBTB1 (Affinity Capture-MS), RCBTB1 (Affinity Capture-MS), ANKRD40 (Affinity Capture-MS), RCBTB1 (Affinity Capture-MS), RCBTB1 (Affinity Capture-MS), RCBTB1 (Affinity Capture-MS), RCBTB1 (Co-fractionation), TOMM22 (Co-fractionation), RCBTB1 (Affinity Capture-MS), ANKRD40 (Affinity Capture-MS), RCBTB1 (Affinity Capture-MS), RCBTB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Q1W5, A6QQY2, B0WWP2, D3Z8N4, E0CZ16, E1B932, E7F6F9, E9Q4F2, F1LZ52, F1LZF0, F1MBP6, O94889, O95198, P57790, Q08DK3, Q14145, Q2T9Z7, Q53G59, Q5R774, Q5R7B8, Q5REP9, Q5U374, Q5ZKD9, Q5ZLD3, Q684M4, Q6DFF6, Q6JEL2, Q6JEL3, Q6NRH0, Q6P798, Q6TDP3, Q6TDP4, Q6ZPT1, Q80TF4, Q8BZM0, Q8JZP3, Q8K430, Q8NDN9, Q8R2H4, Q8VCK5

Diamond homologs: A6NED2, D3ZGQ5, F1RD40, O75592, O95199, O95714, P0C5Y8, P18754, P23800, P25171, P25183, P58544, Q15034, Q15751, Q4R828, Q4U2R1, Q52KW8, Q5BIW4, Q5DX34, Q5GLZ8, Q5PQN1, Q5RCZ7, Q6NRS1, Q6NXM2, Q6NYE2, Q6PAV2, Q6ZPR6, Q7TPH6, Q7ZZC8, Q86SG6, Q8BK67, Q8BTU7, Q8IVU3, Q8K1R7, Q8K2J9, Q8NDN9, Q8SSY6, Q8TD19, Q8VE37, Q90XC2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Macroautophagy	6	23.1×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	6	45.4×	7e-07
intrinsic apoptotic signaling pathway	5	42.7×	9e-06
autophagosome maturation	5	41.8×	9e-06
G1/S transition of mitotic cell cycle	6	28.7×	8e-06
autophagosome assembly	5	26.8×	7e-05
proteasome-mediated ubiquitin-dependent protein catabolic process	6	7.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	12
Uncertain significance	199
Likely benign	153
Benign	49

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074907	NM_018191.4(RCBTB1):c.1028G>A (p.Trp343Ter)	Pathogenic
1076839	NM_018191.4(RCBTB1):c.1320dup (p.Ile441fs)	Pathogenic
1361522	NM_018191.4(RCBTB1):c.364dup (p.Cys122fs)	Pathogenic
1415753	NM_018191.4(RCBTB1):c.1086_1089del (p.Lys362fs)	Pathogenic
1423405	NM_018191.4(RCBTB1):c.770G>A (p.Trp257Ter)	Pathogenic
1446308	NM_018191.4(RCBTB1):c.621C>A (p.Tyr207Ter)	Pathogenic
1453754	NM_018191.4(RCBTB1):c.47_48del (p.Gln16fs)	Pathogenic
1456024	NM_018191.4(RCBTB1):c.1115_1118dup (p.Lys373fs)	Pathogenic
1457323	NM_018191.4(RCBTB1):c.377_378insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGGTGTGGTAGTCTCGAGTTTGATAGGGTGACGCGAGAGGTAGTGGGAGACGGGAGAGGGAGAGGGAGACGGGAGAGGGAGAGGGAGCTGTACCAATCTCTT (p.Leu126delinsPhePhePhePhePhePhePheXaaXaaXaaXaaValTrpTer)	Pathogenic
1460370	NC_000013.10:g.(?50125442)(50126441_?)del	Pathogenic
1960457	NM_018191.4(RCBTB1):c.514C>T (p.Arg172Ter)	Pathogenic
1966120	NM_018191.4(RCBTB1):c.1123C>T (p.Arg375Ter)	Pathogenic
2030962	NM_018191.4(RCBTB1):c.92_105del (p.Ala31fs)	Pathogenic
2834248	NM_018191.4(RCBTB1):c.1262_1263del (p.Tyr421fs)	Pathogenic
3248701	NM_018191.4(RCBTB1):c.1243C>T (p.Gln415Ter)	Pathogenic
4780421	NM_018191.4(RCBTB1):c.383del (p.Lys128fs)	Pathogenic
4805149	NM_018191.4(RCBTB1):c.1073_1074del (p.Glu358fs)	Pathogenic
830904	NC_000013.11:g.(?49559918)(49560084_?)del	Pathogenic
957270	NM_018191.4(RCBTB1):c.358C>T (p.Gln120Ter)	Pathogenic
971441	NM_018191.4(RCBTB1):c.1025C>T (p.Ser342Leu)	Pathogenic
971442	NM_018191.4(RCBTB1):c.634C>T (p.Gln212Ter)	Pathogenic
1067031	NM_018191.4(RCBTB1):c.436_444+14del	Likely pathogenic
1299911	NM_018191.4(RCBTB1):c.854+1G>T	Likely pathogenic
1678104	NM_018191.4(RCBTB1):c.797del (p.Gly266fs)	Likely pathogenic
224621	NM_018191.4(RCBTB1):c.1172+1G>A	Likely pathogenic
253018	NM_018191.4(RCBTB1):c.973C>T (p.His325Tyr)	Likely pathogenic
2841902	NM_018191.4(RCBTB1):c.1325-1G>A	Likely pathogenic
3249579	NM_018191.4(RCBTB1):c.1325-2A>G	Likely pathogenic
3686838	NM_018191.4(RCBTB1):c.711+1G>C	Likely pathogenic
4086015	GRCh37/hg19 13q14.2(chr13:50123594-50173237)x4	Likely pathogenic

SpliceAI

1923 predictions. Top by Δscore:

Variant	Effect	Δscore
13:49541007:CTAAA:C	acceptor_loss	1.0000
13:49541823:CACAC:C	acceptor_gain	1.0000
13:49541825:CAC:C	acceptor_gain	1.0000
13:49541826:ACCT:A	acceptor_loss	1.0000
13:49541835:A:T	acceptor_gain	1.0000
13:49544775:T:A	donor_gain	1.0000
13:49547066:T:C	donor_gain	1.0000
13:49549644:CCACC:C	acceptor_gain	1.0000
13:49549645:CACCC:C	acceptor_gain	1.0000
13:49549647:CC:C	acceptor_gain	1.0000
13:49549648:CC:C	acceptor_gain	1.0000
13:49550474:A:C	acceptor_gain	1.0000
13:49551321:GTTAC:G	donor_loss	1.0000
13:49551322:TTA:T	donor_loss	1.0000
13:49551323:TACCT:T	donor_loss	1.0000
13:49551324:A:AG	donor_loss	1.0000
13:49551325:C:CT	donor_loss	1.0000
13:49551325:CCTTT:C	donor_gain	1.0000
13:49551465:CAAT:C	acceptor_gain	1.0000
13:49552173:CGTA:C	donor_loss	1.0000
13:49552174:GTAC:G	donor_loss	1.0000
13:49552175:TACC:T	donor_loss	1.0000
13:49552176:A:AG	donor_loss	1.0000
13:49552177:C:CA	donor_loss	1.0000
13:49552285:CC:C	acceptor_loss	1.0000
13:49552285:CCT:C	acceptor_gain	1.0000
13:49552286:C:CA	acceptor_loss	1.0000
13:49552287:T:C	acceptor_gain	1.0000
13:49552287:T:TC	acceptor_gain	1.0000
13:49555509:CCTCA:C	donor_loss	1.0000

AlphaMissense

3477 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:49549575:A:G	W310R	1.000
13:49549575:A:T	W310R	1.000
13:49551411:A:G	W257R	1.000
13:49551411:A:T	W257R	1.000
13:49552272:C:T	G206D	1.000
13:49552273:C:G	G206R	1.000
13:49552276:A:G	W205R	1.000
13:49552276:A:T	W205R	1.000
13:49555636:C:T	G161E	1.000
13:49555645:C:T	G158D	1.000
13:49555653:G:C	N155K	1.000
13:49555653:G:T	N155K	1.000
13:49555660:C:A	G153V	1.000
13:49555660:C:T	G153D	1.000
13:49555661:C:G	G153R	1.000
13:49555664:A:G	W152R	1.000
13:49555664:A:T	W152R	1.000
13:49560039:C:T	G108E	1.000
13:49560040:C:A	G108W	1.000
13:49560067:A:G	W99R	1.000
13:49560067:A:T	W99R	1.000
13:49534150:G:T	A523D	0.999
13:49540895:G:T	A479E	0.999
13:49540896:C:G	A479P	0.999
13:49540954:A:C	C459W	0.999
13:49540991:G:T	A447E	0.999
13:49540992:C:G	A447P	0.999
13:49540994:A:G	L446S	0.999
13:49541000:A:G	L444P	0.999
13:49541003:A:G	L443P	0.999

dbSNP variants (sampled 300 via entrez): RS1000097121 (13:49568928 G>A), RS1000119142 (13:49539488 C>G,T), RS1000162152 (13:49571502 C>T), RS1000189179 (13:49550347 A>G,T), RS1000230478 (13:49561858 G>A), RS1000445593 (13:49584312 T>C), RS1000451634 (13:49531601 C>T), RS1000496911 (13:49572891 T>C), RS1000537941 (13:49555483 T>C,G), RS1000586445 (13:49531852 C>T), RS1000644636 (13:49532875 T>TA), RS1000655758 (13:49585525 G>A,C), RS1000697612 (13:49544303 C>G), RS1000714016 (13:49579561 T>C), RS1000746939 (13:49579780 G>A)

Disease associations

OMIM: gene MIM:607867 | disease phenotypes: MIM:617175, MIM:300216, MIM:133780, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
RCBTB1-related retinopathy	Strong	Autosomal recessive
reticular dystrophy of the retinal pigment epithelium	Supportive	Autosomal recessive
exudative vitreoretinopathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
RCBTB1-related retinopathy	Definitive	AR

Mondo (6): inherited retinal dystrophy (MONDO:0019118), RCBTB1-related retinopathy (MONDO:0014955), Coats disease (MONDO:0010269), exudative vitreoretinopathy (MONDO:0019516), retinitis pigmentosa (MONDO:0019200), reticular dystrophy of the retinal pigment epithelium (MONDO:0009979)

Orphanet (4): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Coats disease (Orphanet:190), Familial exudative vitreoretinopathy (Orphanet:891), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000556	Retinal dystrophy
HP:0000853	Goiter
HP:0000869	Secondary amenorrhea
HP:0001256	Mild intellectual disability
HP:0002206	Pulmonary fibrosis
HP:0003581	Adult onset
HP:0003621	Juvenile onset
HP:0007663	Reduced visual acuity
HP:0008209	Premature ovarian insufficiency

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST002715_4	Breastfeeding duration	2.000000e-06
GCST004613_35	Sum neutrophil eosinophil counts	5.000000e-10
GCST004614_14	Granulocyte count	7.000000e-10
GCST004620_83	Sum basophil neutrophil counts	2.000000e-09
GCST004625_137	Monocyte count	6.000000e-12
GCST004626_124	Myeloid white cell count	8.000000e-11
GCST004629_134	Neutrophil count	1.000000e-09
GCST006291_68	Spherical equivalent or myopia (age of diagnosis)	3.000000e-10
GCST010002_186	Refractive error	1.000000e-36
GCST011096_30	Systemic lupus erythematosus	4.000000e-08
GCST011768_19	Schizophrenia	2.000000e-08
GCST90002389_475	Lymphocyte percentage of white cells	1.000000e-10
GCST90002393_294	Monocyte count	1.000000e-20
GCST90002398_211	Neutrophil count	4.000000e-21
GCST90002407_607	White blood cell count	2.000000e-22
GCST90011866_19	Systemic lupus erythematosus	1.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006864	breastfeeding duration
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0004847	age at onset
EFO:0007993	lymphocyte percentage of leukocytes

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D058456	Retinal Telangiectasis	C11.768.748; C14.907.823.502
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C566721	Reticular Dystrophy Of Retinal Pigment Epithelium (supp.)
C564844	Retinal Dystrophy, Reticular Pigmentary, of Posterior Pole (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, decreases methylation	1
sodium arsenite	increases expression	1
manganese chloride	increases expression, increases abundance	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
abrine	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Allergens	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Coumestrol	decreases expression	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Fluoxetine	increases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Mitoxantrone	affects response to substance	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	affects expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_XI39	LEIi011-A	Induced pluripotent stem cell	Female
CVCL_XI40	LEIi011-B	Induced pluripotent stem cell	Female
CVCL_XI41	LEIi011-C	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06520410	PHASE4	RECRUITING	Safety and Efficacy of 18 mm Short Vitrectomy Probe for Pediatric Vitreoretinal Surgeries
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
NCT03940690	PHASE3	TERMINATED	Interest of Intravitreal Injections of Anti-VEGF as Initial and Adjuvant Treatment in Coats Disease
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
NCT05107921	PHASE2	UNKNOWN	Bromfenac Sodium Hydrate Eye Drops in Familial Exudative Vitreoretinopathy
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)