RAB28

Summary

RAB28 (RAB28, member RAS oncogene family, HGNC:9768) is a protein-coding gene on chromosome 4p15.33, encoding Ras-related protein Rab-28 (P51157). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

This gene encodes a member of the Rab subfamily of Ras-related small GTPases. The encoded protein may be involved in regulating intracellular trafficking. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 9 and X.

Source: NCBI Gene 9364 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RAB28-related retinopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 190 total — 13 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 23
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001017979

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9768
Approved symbol	RAB28
Name	RAB28, member RAS oncogene family
Location	4p15.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000157869
Ensembl biotype	protein_coding
OMIM	612994
Entrez	9364

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 nonsense_mediated_decay

ENST00000288723, ENST00000330852, ENST00000338176, ENST00000504644, ENST00000508274, ENST00000510528, ENST00000511649, ENST00000630951, ENST00000896235, ENST00000896236, ENST00000926296

RefSeq mRNA: 3 — MANE Select: NM_001017979 NM_001017979, NM_001159601, NM_004249

CCDS: CCDS33961, CCDS3409, CCDS54741

Canonical transcript exons

ENST00000330852 — 7 exons

Exon	Start	End
ENSE00001035589	13460699	13460828
ENSE00001035594	13479430	13479526
ENSE00001035607	13474318	13474406
ENSE00003476950	13376545	13376622
ENSE00003632351	13381491	13381594
ENSE00003691331	13367724	13368650
ENSE00003843609	13484076	13484340

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8163 / max 75.1101, expressed in 1725 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51407	6.8163	1725

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.12	gold quality
germinal epithelium of ovary	UBERON:0001304	97.62	gold quality
endothelial cell	CL:0000115	96.92	gold quality
visceral pleura	UBERON:0002401	96.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.83	gold quality
parietal pleura	UBERON:0002400	96.58	gold quality
oocyte	CL:0000023	96.37	gold quality
bronchial epithelial cell	CL:0002328	96.20	gold quality
medial globus pallidus	UBERON:0002477	95.78	gold quality
secondary oocyte	CL:0000655	95.74	gold quality
adult organism	UBERON:0007023	95.64	gold quality
pleura	UBERON:0000977	95.45	gold quality
globus pallidus	UBERON:0001875	95.33	gold quality
middle temporal gyrus	UBERON:0002771	94.99	gold quality
sperm	CL:0000019	94.85	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.59	gold quality
epithelium of nasopharynx	UBERON:0001951	94.31	gold quality
lateral globus pallidus	UBERON:0002476	94.02	gold quality
amniotic fluid	UBERON:0000173	94.01	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.87	gold quality
gingival epithelium	UBERON:0001949	93.35	gold quality
pigmented layer of retina	UBERON:0001782	92.61	gold quality
retina	UBERON:0000966	92.58	gold quality
cartilage tissue	UBERON:0002418	92.50	gold quality
corpus callosum	UBERON:0002336	92.47	gold quality
substantia nigra pars compacta	UBERON:0001965	92.44	gold quality
male germ cell	CL:0000015	92.43	gold quality
caput epididymis	UBERON:0004358	92.26	gold quality
esophagus squamous epithelium	UBERON:0006920	92.22	gold quality
subthalamic nucleus	UBERON:0001906	92.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting RAB28, 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-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-7151-3P	99.04	69.72	2370

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 7)

• Crystal structures of Rab28 in the active (GppNHp-bound) and inactive (GDP-3’P-bound) forms at 1.5 and 1.1A resolution were reported. (PMID:19026641)
• Autosomal-recessive cone-rod dystrophy is associated with RAB28 mutations. (PMID:23746546)
• Deleterious mutations in RAB28 result in a classic CRD phenotype and are an infrequent cause of CRD in the Spanish population. (PMID:25356532)
• In summary, we identified a novel rare “likely pathogenic” variant–RAB28 c.68C>T–in a Korean patient with cone-rod dystrophy. (PMID:28388261)
• In conclusion, RAB28 variants are a rare cause of cone-rod dystrophy in various ethnic groups. These variants cause a comparable ophthalmological phenotype and furthermore could also be a cause of postaxial polydactyly. (PMID:32084271)
• Expanding the Clinical and Genetic Spectrum of RAB28-Related Cone-Rod Dystrophy: Pathogenicity of Novel Variants in Italian Families. (PMID:33396523)
• The roles of Klotho and FGF-23 in bipolar manic episode. (PMID:37869955)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rab28	ENSMUSG00000029128

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), RAB21 (ENSG00000080371), RAB10 (ENSG00000084733), RAB18 (ENSG00000099246), RAB36 (ENSG00000100228), IFT27 (ENSG00000100360), RAB40AL (ENSG00000102128), RAB11A (ENSG00000103769), RAB2A (ENSG00000104388), RAB3D (ENSG00000105514), RAB3A (ENSG00000105649), RAB5C (ENSG00000108774), RAB34 (ENSG00000109113), RAB5B (ENSG00000111540), RAB35 (ENSG00000111737), RAB23 (ENSG00000112210), DNAJC27 (ENSG00000115137), RAB29 (ENSG00000117280), RAB32 (ENSG00000118508), RAB14 (ENSG00000119396), RAB9B (ENSG00000123570), RAB9A (ENSG00000123595), RAB38 (ENSG00000123892), RAB22A (ENSG00000124209), RAB17 (ENSG00000124839), RAB2B (ENSG00000129472), RAB25 (ENSG00000132698), RAB33A (ENSG00000134594), RAB30 (ENSG00000137502), RAB1A (ENSG00000138069), RAB20 (ENSG00000139832), RAB15 (ENSG00000139998), RAB40B (ENSG00000141542), RAB13 (ENSG00000143545), RABL2A (ENSG00000144134), RAB5A (ENSG00000144566), RAB19 (ENSG00000146955)

Protein

Protein identifiers

Ras-related protein Rab-28 — P51157 (reviewed: P51157)

All UniProt accessions (5): P51157, H0Y927, H0Y9G4, H0Y9S6, Q8WVF3

UniProt curated annotations — full annotation on UniProt →

Function. The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB28 is required for shedding and phagocytosis of cone cell outer segments (OS) discs in the retina. Also participates in nuclear factor kappa-B p65/RELA nuclear transport in endothelial cells.

Subunit / interactions. Interacts (prenylated form) with PDE6D; the interaction promotes RAB28 delivery to the photoreceptor outer segments. Interacts with KCNJ13; the interaction may facilitate cone outer segments phagocytosis. Interacts with RELA; the interaction contributes to RELA transport from cytoplasm to nucleus.

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton. Cilium basal body. Nucleus.

Tissue specificity. Isoform S is detected in most tissues investigated: cortex, liver, kidney, skeletal muscle, adipose tissue, testis, urothelium, lung, bone marrow and retinal pigment epithelium (RPE). Isoform L 2 is widely and abundantly expressed all tissues. Isoform 3 is highly expressed in heart, lung, bone marrow, retina, brain, and RPE.

Post-translational modifications. Isoprenylated.

Disease relevance. Cone-rod dystrophy 18 (CORD18) [MIM:615374] 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.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP. Regulated by GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity. Inhibited by GDP dissociation inhibitors (GDIs).

Domain organisation. Switch I, switch II and the interswitch regions are characteristic of Rab GTPases and mediate the interactions with Rab downstream effectors. The switch regions undergo conformational changes upon nucleotide binding which drive interaction with specific sets of effector proteins, with most effectors only binding to GTP-bound Rab.

Similarity. Belongs to the small GTPase superfamily. Rab family.

Isoforms (3)

UniProt ID	Names	Canonical?
P51157-1	S, Rab28S	yes
P51157-2	L, Rab28L
P51157-3	3

RefSeq proteins (3): NP_001017979, NP_001153073, NP_004240 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (49 total): binding site 18, helix 10, strand 6, modified residue 3, turn 3, splice variant 2, region of interest 2, initiator methionine 1, chain 1, propeptide 1, lipid moiety-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2HXS	X-RAY DIFFRACTION	1.1
3E5H	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51157-F1	84.41	0.63

Functional residue map

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

Ligand- & substrate-binding residues (18): 27; 38; 39; 41; 44; 44; 68; 71; 129; 130; 132; 160 …

Post-translational modifications (4): 2, 8, 218, 218

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 149 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, YY1_Q6, GOCC_MICROTUBULE_ORGANIZING_CENTER, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GGTGAAG_MIR412, BIDUS_METASTASIS_UP, GCCATNTTG_YY1_Q6, GOCC_CILIUM, GOCC_CILIARY_BASAL_BODY, GOMF_GTPASE_ACTIVITY, GOMF_GDP_BINDING, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, chr4p15, COLINA_TARGETS_OF_4EBP1_AND_4EBP2

GO Biological Process (2): intracellular protein transport (GO:0006886), protein transport (GO:0015031)

GO Molecular Function (8): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (14): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), endomembrane system (GO:0012505), ciliary rootlet (GO:0035253), ciliary basal body (GO:0036064), endosome (GO:0005768), late endosome (GO:0005770), cytoskeleton (GO:0005856), endosome membrane (GO:0010008), membrane (GO:0016020), phagocytic vesicle membrane (GO:0030670), cell projection (GO:0042995), bounding membrane of organelle (GO:0098588)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular protein localization	2
guanyl ribonucleotide binding	2
cilium	2
endosome	2
protein transport	1
intracellular transport	1
transport	1
establishment of protein localization	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1
cytoskeleton	1
microtubule organizing center	1
endomembrane system	1
cytoplasmic vesicle	1
intracellular membraneless organelle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
endocytic vesicle membrane	1
phagocytic vesicle	1
organelle membrane	1

Protein interactions and networks

STRING

1512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB28	CFAP418	Q96NL8	619
RAB28	ZNF653	Q96CK0	570
RAB28	ARF1	P10947	540
RAB28	ARL3	P36405	519
RAB28	TTLL5	Q6EMB2	519
RAB28	POC1B	Q8TC44	495
RAB28	RPGRIP1	Q96KN7	491
RAB28	TTLL10	Q6ZVT0	482
RAB28	CDHR1	Q96JP9	478
RAB28	PITPNM3	Q9BZ71	462
RAB28	FRMPD1	Q5SYB0	458
RAB28	IFT22	Q9H7X7	456
RAB28	PDE6D	O43924	455
RAB28	DENND5A	Q6IQ26	449
RAB28	DENND1C	Q8IV53	448

IntAct

24 interactions, top by confidence:

A	B	Type	Score
PDE6D	ARL3	psi-mi:“MI:0914”(association)	0.920
FBXO42	GSK3A	psi-mi:“MI:0914”(association)	0.660
RAB28	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
RAB28	ACSF3	psi-mi:“MI:0915”(physical association)	0.560
MNS1	RAB28	psi-mi:“MI:0914”(association)	0.510
RAB28	CCDC144A	psi-mi:“MI:0914”(association)	0.510
FBXO42	CST1	psi-mi:“MI:0914”(association)	0.350
PDE6D	SUN1	psi-mi:“MI:0914”(association)	0.350
RAB28	RAD17	psi-mi:“MI:0914”(association)	0.350
PDE6D	UBL3	psi-mi:“MI:0914”(association)	0.350
SLC38A5	NRP1	psi-mi:“MI:0914”(association)	0.350
RAB28	CCDC144A	psi-mi:“MI:0915”(physical association)	0.000
RAB28	PDE6D	psi-mi:“MI:0915”(physical association)	0.000
RAB28	CTSV	psi-mi:“MI:0915”(physical association)	0.000
RAB28	HMMR	psi-mi:“MI:0915”(physical association)	0.000
RAB28	HSF1	psi-mi:“MI:0915”(physical association)	0.000
RAB28	KIF7	psi-mi:“MI:0915”(physical association)	0.000
RAB28	MNS1	psi-mi:“MI:0915”(physical association)	0.000
RAB28	NCOA3	psi-mi:“MI:0915”(physical association)	0.000
RAB28	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.000
ACSF3	RAB28	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): RAB28 (Affinity Capture-MS), RAB28 (Affinity Capture-MS), RAB28 (Affinity Capture-MS), PDE6D (Affinity Capture-MS), NCOA3 (Affinity Capture-MS), CTSV (Affinity Capture-MS), CCDC144A (Affinity Capture-MS), HMMR (Affinity Capture-MS), KIF7 (Affinity Capture-MS), HSF1 (Affinity Capture-MS), MNS1 (Affinity Capture-MS), RAB28 (Affinity Capture-RNA), PLEKHF2 (Two-hybrid), ACSF3 (Two-hybrid), RAB28 (Affinity Capture-MS)

ESM2 similar proteins: A1DZY4, A6QP66, O35626, O35929, O88910, O88954, P0C0E4, P35295, P51157, P51158, P53667, P53668, P53669, P55040, P55041, P55043, P63032, P63033, Q06AU5, Q12829, Q13368, Q13637, Q3SWY9, Q5E9J3, Q5FVY2, Q5R541, Q5RFI2, Q6DGN0, Q6IMA3, Q6IMA7, Q6IMB1, Q6P0U3, Q6T310, Q8AVS6, Q8IYK8, Q8QFP8, Q8VEL9, Q8VHP8, Q8VHQ4, Q8WXH6

Diamond homologs: A4IHM6, F1PTE3, F4KFD8, O13876, O23657, O49841, P35286, P51153, P51157, P51158, P51159, Q14964, Q17QU4, Q18969, Q32LJ6, Q3SWY9, Q58DS5, Q5HYI8, Q5KTJ6, Q5RFI2, Q5UQ27, Q5ZKR4, Q6GPS4, Q6TNS7, Q7T3A4, Q7Z6P3, Q8BHC1, Q8BHD0, Q8N4Z0, Q948K8, Q96DA2, Q99KL7, Q9C5J9, Q9D4V7, Q9DD03, Q9SJ11, C8VQY7, O01803, O04157, O04486

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	5
Uncertain significance	82
Likely benign	66
Benign	10

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
1001199	NM_001017979.3(RAB28):c.435dup (p.Arg146fs)	Pathogenic
1009564	NM_001017979.3(RAB28):c.131_132del (p.Thr44fs)	Pathogenic
1481177	NM_001017979.3(RAB28):c.549_552del (p.Asn183fs)	Pathogenic
1502408	NM_001017979.3(RAB28):c.90del (p.Cys31fs)	Pathogenic
2093933	NM_004249.4(RAB28):c.603_615del (p.Lys200_Tyr201insTer)	Pathogenic
225878	NM_001017979.3(RAB28):c.172+1G>C	Pathogenic
2772471	NM_001017979.3(RAB28):c.234del (p.Met78fs)	Pathogenic
3250323	NC_000004.12:g.(?13369875)(13381595_13460698)del	Pathogenic
3363160	NM_001017979.3(RAB28):c.247_248dup (p.Tyr84fs)	Pathogenic
4076067	GRCh37/hg19 4p15.33(chr4:13410293-13468118)x1	Pathogenic
60754	NM_001017979.3(RAB28):c.565C>T (p.Gln189Ter)	Pathogenic
60755	NM_001017979.3(RAB28):c.409C>T (p.Arg137Ter)	Pathogenic
839900	NM_001017979.3(RAB28):c.76-9A>G	Pathogenic
1953562	NM_004249.4(RAB28):c.574-1G>A	Likely pathogenic
2577489	NM_001017979.3(RAB28):c.430C>T (p.His144Tyr)	Likely pathogenic
4849230	NM_001017979.3(RAB28):c.128_131del (p.Gln43fs)	Likely pathogenic
623218	NM_001017979.3(RAB28):c.355_356del (p.Glu119fs)	Likely pathogenic
866668	NM_001017979.3(RAB28):c.502del (p.Leu168fs)	Likely pathogenic

SpliceAI

2039 predictions. Top by Δscore:

Variant	Effect	Δscore
4:13381482:TTTAC:T	donor_loss	1.0000
4:13381483:TTAC:T	donor_loss	1.0000
4:13381484:TACTT:T	donor_loss	1.0000
4:13381485:ACTT:A	donor_loss	1.0000
4:13381487:T:TA	donor_loss	1.0000
4:13381488:T:TC	donor_loss	1.0000
4:13381489:A:AC	donor_gain	1.0000
4:13381489:A:AG	donor_loss	1.0000
4:13381490:C:CA	donor_gain	1.0000
4:13381490:CA:C	donor_gain	1.0000
4:13381591:TCAA:T	acceptor_gain	1.0000
4:13381592:CAA:C	acceptor_gain	1.0000
4:13381592:CAAC:C	acceptor_gain	1.0000
4:13381593:AA:A	acceptor_gain	1.0000
4:13381595:C:CC	acceptor_gain	1.0000
4:13381603:G:C	acceptor_gain	1.0000
4:13381603:G:GC	acceptor_gain	1.0000
4:13381605:G:C	acceptor_gain	1.0000
4:13425228:C:CC	acceptor_gain	1.0000
4:13460697:A:AC	donor_gain	1.0000
4:13460698:C:CC	donor_gain	1.0000
4:13479527:C:CC	acceptor_gain	1.0000
4:13369984:A:C	acceptor_gain	0.9900
4:13380630:T:TA	donor_gain	0.9900
4:13380667:CAATG:C	donor_gain	0.9900
4:13381490:CAGA:C	donor_gain	0.9900
4:13381590:ATCAA:A	acceptor_gain	0.9900
4:13381594:ACTA:A	acceptor_loss	0.9900
4:13381595:CTAG:C	acceptor_loss	0.9900
4:13381596:T:C	acceptor_loss	0.9900

AlphaMissense

1454 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:13460701:T:A	K130I	1.000
4:13460700:T:A	K130N	0.999
4:13460700:T:G	K130N	0.999
4:13474376:T:G	D68A	0.999
4:13474377:C:G	D68H	0.999
4:13376595:C:G	A175P	0.998
4:13376597:G:T	A174D	0.998
4:13381507:G:T	A160D	0.998
4:13460702:T:C	K130E	0.998
4:13460707:C:T	G128D	0.998
4:13460790:G:C	S100R	0.998
4:13460790:G:T	S100R	0.998
4:13460792:T:G	S100R	0.998
4:13474375:A:C	D68E	0.998
4:13474375:A:T	D68E	0.998
4:13474376:T:A	D68V	0.998
4:13474376:T:C	D68G	0.998
4:13479525:G:A	T26I	0.998
4:13484080:C:T	G24E	0.998
4:13484081:C:A	G24W	0.998
4:13484095:C:T	G19E	0.998
4:13484096:C:A	G19W	0.998
4:13381511:A:G	S159P	0.997
4:13381513:A:T	V158D	0.997
4:13460701:T:G	K130T	0.997
4:13460703:A:C	N129K	0.997
4:13460703:A:T	N129K	0.997
4:13460710:A:T	V127E	0.997
4:13460771:A:G	W107R	0.997
4:13460771:A:T	W107R	0.997

dbSNP variants (sampled 300 via entrez): RS1000017344 (4:13420412 C>G), RS1000025006 (4:13392774 A>G), RS1000037647 (4:13459011 A>G), RS1000050279 (4:13411899 A>C), RS1000075958 (4:13393006 T>G), RS1000093737 (4:13467294 G>A,T), RS1000104459 (4:13460259 G>T), RS10001114 (4:13367991 T>C), RS1000118677 (4:13385288 C>A), RS10001262 (4:13392259 T>A,C), RS1000166966 (4:13415132 T>A,C), RS1000180776 (4:13483039 G>A), RS10001828 (4:13368968 A>C), RS1000213570 (4:13452103 C>T), RS1000221658 (4:13377056 T>A)

Disease associations

OMIM: gene MIM:612994 | disease phenotypes: MIM:615374, MIM:120970, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
cone-rod dystrophy 18	Definitive	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
RAB28-related retinopathy	Definitive	AR

Mondo (5): cone-rod dystrophy 18 (MONDO:0014153), inherited retinal dystrophy (MONDO:0019118), cone-rod dystrophy (MONDO:0015993), cone dystrophy (MONDO:0000455), retinitis pigmentosa (MONDO:0019200)

Orphanet (4): Cone rod dystrophy (Orphanet:1872), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Progressive cone dystrophy (Orphanet:1871), Retinitis pigmentosa (Orphanet:791)

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:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0001105	Retinal atrophy
HP:0003621	Juvenile 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:0008001	Foveal hyperpigmentation
HP:0011003	High myopia
HP:0011463	Childhood onset
HP:0012508	Metamorphopsia
HP:0025010	Foveal atrophy
HP:0030466	Abnormal full-field electroretinogram
HP:0000556	Retinal dystrophy

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001762_856	Obesity-related traits	6.000000e-06
GCST002312_4	Periodontal disease-related phenotype (Socransky)	1.000000e-06
GCST002312_7	Periodontal disease-related phenotype (Socransky)	4.000000e-06
GCST002647_21	Height	8.000000e-13
GCST006979_324	Heel bone mineral density	3.000000e-09
GCST007687_3	Photic sneeze reflex	2.000000e-08
GCST008839_524	Height	2.000000e-10
GCST011536_12	Intestinal permeability measurement	2.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0009270	heel bone mineral density
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0011031	intestinal permeability measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D000077765	Cone Dystrophy	C11.270.151; C11.768.216
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, increases expression, affects expression	3
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylselenic acid	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
2-palmitoylglycerol	increases expression	1
pomalidomide	increases degradation, decreases expression	1
Lenalidomide	decreases expression, increases degradation	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	decreases expression	1
Quercetin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
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]
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration