DRAM2

Summary

DRAM2 (DNA damage regulated autophagy modulator 2, HGNC:28769) is a protein-coding gene on chromosome 1p13.3, encoding DNA damage-regulated autophagy modulator protein 2 (Q6UX65). Plays a role in the initiation of autophagy.

The protein encoded by this gene binds microtubule-associated protein 1 light chain 3 and is required for autophagy. Defects in this gene are a cause of retinal dystrophy. In addition, two microRNAs (microRNA 125b-1 and microRNA 144) can bind to the mRNA of this gene and produce the disease state.

Source: NCBI Gene 128338 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cone-rod dystrophy 21 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 220 total — 21 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 20
• MANE Select transcript: NM_001349884

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28769
Approved symbol	DRAM2
Name	DNA damage regulated autophagy modulator 2
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC54289, PRO180, WWFQ154, RP5-1180E21.1
Ensembl gene	ENSG00000156171
Ensembl biotype	protein_coding
OMIM	613360
Entrez	128338

Gene structure

Transcript identifiers

Ensembl transcripts: 63 — 56 protein_coding, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000286692, ENST00000461449, ENST00000463682, ENST00000477588, ENST00000477769, ENST00000480600, ENST00000484310, ENST00000490780, ENST00000496430, ENST00000539140, ENST00000875066, ENST00000875067, ENST00000875068, ENST00000875069, ENST00000875070, ENST00000875071, ENST00000875072, ENST00000875073, ENST00000875074, ENST00000875075, ENST00000875076, ENST00000875077, ENST00000875078, ENST00000875079, ENST00000875080, ENST00000875081, ENST00000875082, ENST00000875083, ENST00000875084, ENST00000875085, ENST00000875086, ENST00000875087, ENST00000875088, ENST00000875089, ENST00000875090, ENST00000875091, ENST00000875092, ENST00000875093, ENST00000875094, ENST00000875095, ENST00000875096, ENST00000875097, ENST00000875098, ENST00000875099, ENST00000933768, ENST00000933769, ENST00000933770, ENST00000933771, ENST00000933772, ENST00000933773, ENST00000933774, ENST00000933775, ENST00000933776, ENST00000933777, ENST00000933778, ENST00000933779, ENST00000933780, ENST00000933781, ENST00000944783, ENST00000944784, ENST00000944785, ENST00000944786, ENST00000944787

RefSeq mRNA: 13 — MANE Select: NM_001349884 NM_001349881, NM_001349882, NM_001349884, NM_001349885, NM_001349886, NM_001349887, NM_001349888, NM_001349889, NM_001349890, NM_001349891, NM_001349892, NM_001349893, NM_178454

CCDS: CCDS30801

Canonical transcript exons

ENST00000484310 — 10 exons

Exon	Start	End
ENSE00001432611	111137523	111137586
ENSE00001905298	111139501	111139666
ENSE00001908527	111140038	111140093
ENSE00003475123	111131424	111131568
ENSE00003515834	111119877	111119959
ENSE00003519402	111120516	111120693
ENSE00003555845	111118805	111118897
ENSE00003683403	111124742	111124881
ENSE00003686443	111126227	111126294
ENSE00003692470	111117163	111118267

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 97.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.8659 / max 442.4410, expressed in 1818 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13796	28.9718	1810
13798	2.8340	1425
13797	2.0188	1272
13799	1.5339	907
13793	0.7321	203
13795	0.5397	247
13794	0.2357	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.53	gold quality
leukocyte	CL:0000738	97.44	gold quality
spleen	UBERON:0002106	97.43	gold quality
oviduct epithelium	UBERON:0004804	97.25	gold quality
ileal mucosa	UBERON:0000331	96.77	gold quality
right uterine tube	UBERON:0001302	96.66	gold quality
vermiform appendix	UBERON:0001154	96.60	gold quality
gall bladder	UBERON:0002110	96.57	gold quality
lymph node	UBERON:0000029	96.40	gold quality
granulocyte	CL:0000094	96.38	gold quality
rectum	UBERON:0001052	95.99	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.91	gold quality
mucosa of stomach	UBERON:0001199	94.99	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.96	gold quality
omental fat pad	UBERON:0010414	94.92	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.91	gold quality
peritoneum	UBERON:0002358	94.88	gold quality
cartilage tissue	UBERON:0002418	94.75	gold quality
adipose tissue	UBERON:0001013	94.72	gold quality
right lung	UBERON:0002167	94.61	gold quality
minor salivary gland	UBERON:0001830	94.59	gold quality
body of pancreas	UBERON:0001150	94.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.29	gold quality
small intestine	UBERON:0002108	94.27	gold quality
fallopian tube	UBERON:0003889	94.23	gold quality
transverse colon	UBERON:0001157	94.16	gold quality
bronchial epithelial cell	CL:0002328	93.89	gold quality
mucosa of transverse colon	UBERON:0004991	93.85	gold quality
cerebellar hemisphere	UBERON:0002245	93.84	gold quality
upper lobe of left lung	UBERON:0008952	93.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	1496.64
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
CDKN1A	Repression
RAC1	Activation
RHOA	Activation
RHOB	Repression
RHOC	Activation
ROCK1	Activation
TP53	Repression

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

75 targeting DRAM2, 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-3163	100.00	77.23	8605
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Literature-anchored findings (GeneRIF, showing 10)

• DRAM2 is different from DRAM as it not induced by p53 or p73. DRAM2 is also a lysosomal protein, its overexpression does not modulate autophagy. (PMID:19556885)
• reduced expression of DRAM2 may contribute to enhanced cell survival in tumor cells. (PMID:19895784)
• The expression of damage-regulated autophagy modulator 2 (DRAM2) contributes to autophagy induction. (PMID:21584698)
• Biallelic mutations in the autophagy regulator DRAM2 cause retinal dystrophy with early macular involvement. (PMID:25983245)
• Genetic variants on chromosome 1p13.3 near the damage-regulated autophagy modulator 2 gene DRAM2 associated with Non-ST Elevation Myocardial Infarction (rs656843; odds ratio 1.57, P = 3.11 x 10(-10)) in the case-control analysis. (PMID:26509668)
• Recessive variants in DRAM2, an autophagy regulator gene, have been recently identified as a cause of retinal dystrophy with early macular involvement (PMID:26720460)
• Mycobacterium tuberculosis significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3’-untranslated region of DRAM2. (PMID:27764573)
• Three novel homozygous mutations in the autophagy gene DRAM2 were identified as the molecular cause of disease in the three families: c.518-1G>A, c.628_629insAG and c.693+2T>A. (PMID:31394102)
• Clinical Course and Electron Microscopic Findings in Lymphocytes of Patients with DRAM2-Associated Retinopathy. (PMID:32079136)
• The Clinical Spectrum and Disease Course of DRAM2 Retinopathy. (PMID:35806404)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dram2a	ENSDARG00000043569
danio_rerio	dram2b	ENSDARG00000044241
mus_musculus	Dram2	ENSMUSG00000027900
rattus_norvegicus	Dram2	ENSRNOG00000017744
drosophila_melanogaster	CG4025	FBGN0025624
caenorhabditis_elegans		WBGENE00007878
caenorhabditis_elegans		WBGENE00020967

Paralogs (4): DRAM1 (ENSG00000136048), TMEM150A (ENSG00000168890), TMEM150B (ENSG00000180061), TMEM150C (ENSG00000249242)

Protein

Protein identifiers

DNA damage-regulated autophagy modulator protein 2 — Q6UX65 (reviewed: Q6UX65)

Alternative names: Transmembrane protein 77

All UniProt accessions (2): Q6UX65, S4R2Z2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the initiation of autophagy. In the retina, might be involved in the process of photoreceptor cells renewal and recycling to preserve visual function. Induces apoptotic cell death when coexpressed with DRAM1.

Subcellular location. Lysosome membrane. Photoreceptor inner segment. Apical cell membrane.

Tissue specificity. Expression is down-regulated in ovarian tumors (at protein level). Widely expressed with highest levels in placenta and heart. Expressed in the retina. Not detected in brain or thymus.

Disease relevance. Cone-rod dystrophy 21 (CORD21) [MIM:616502] 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.

Induction. Not induced by p53/TP53 or TP73/p73.

Similarity. Belongs to the DRAM/TMEM150 family.

RefSeq proteins (13): NP_001336810, NP_001336811, NP_001336813, NP_001336814, NP_001336815, NP_001336816, NP_001336817, NP_001336818, NP_001336819, NP_001336820, NP_001336821, NP_001336822, NP_848549 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019402	CWH43_N	Domain
IPR050911	DRAM/TMEM150_Autophagy_Mod	Family

Pfam: PF10277

UniProt features (13 total): transmembrane region 6, sequence variant 5, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UX65-F1	91.35	0.75

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 201 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOCC_VACUOLAR_MEMBRANE, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, TGACCTY_ERR1_Q2, MARTINEZ_RB1_TARGETS_UP, GOBP_REGULATION_OF_CATABOLIC_PROCESS, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOCC_APICAL_PLASMA_MEMBRANE

GO Biological Process (7): autophagy (GO:0006914), apoptotic process (GO:0006915), visual perception (GO:0007601), cell population proliferation (GO:0008283), regulation of autophagy (GO:0010506), photoreceptor cell maintenance (GO:0045494), retina development in camera-type eye (GO:0060041)

GO Molecular Function (0):

GO Cellular Component (9): photoreceptor inner segment (GO:0001917), cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), Golgi apparatus (GO:0005794), apical plasma membrane (GO:0016324), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
sensory perception of light stimulus	1
cellular process	1
autophagy	1
regulation of catabolic process	1
retina homeostasis	1
multicellular organismal process	1
camera-type eye development	1
anatomical structure development	1
intracellular anatomical structure	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
apical part of cell	1
plasma membrane region	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DRAM2	BECN1	Q14457	796
DRAM2	UVRAG	Q9P2Y5	652
DRAM2	PIK3C3	Q8NEB9	494
DRAM2	TTLL5	Q6EMB2	477
DRAM2	TP53	P04637	452
DRAM2	CFAP418	Q96NL8	439
DRAM2	POC1B	Q8TC44	433
DRAM2	RAX2	Q96IS3	432
DRAM2	SIPA1L1	O43166	407
DRAM2	TTLL10	Q6ZVT0	403
DRAM2	RAB28	P51157	363
DRAM2	GPR37L1	O60883	361
DRAM2	CEP78	Q5JTW2	361
DRAM2	ATG12	O94817	357
DRAM2	ISCA1	Q9BUE6	353

IntAct

10 interactions, top by confidence:

A	B	Type	Score
	DENND11	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
LAMP1	DST	psi-mi:“MI:0914”(association)	0.350
SLC19A2	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC35F1	C15orf61	psi-mi:“MI:0914”(association)	0.350
SLC6A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
gptB	DRAM2	psi-mi:“MI:0915”(physical association)	0.000
	DRAM2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): DRAM2 (Synthetic Lethality), DRAM2 (Affinity Capture-MS), DRAM2 (Affinity Capture-MS), DRAM2 (Affinity Capture-MS), DRAM2 (Affinity Capture-MS), DRAM2 (Affinity Capture-MS), DRAM2 (Affinity Capture-MS), DRAM2 (Affinity Capture-MS), DRAM2 (Affinity Capture-RNA), DRAM2 (Affinity Capture-RNA)

ESM2 similar proteins: A2A559, A2V7M9, A6H7B8, A6NC51, A6X919, A7MBB3, A7YWP2, A8KBG2, A8WFS8, A8XST1, A9JSP6, D4AD75, P70245, Q0VFE3, Q22141, Q29M88, Q2ABP2, Q2ABP3, Q2PZI1, Q32PK2, Q3TQR0, Q3ZC48, Q4V7T3, Q4V7T7, Q4VV71, Q568I2, Q5BK09, Q5BL33, Q5EAK8, Q5M9A7, Q60774, Q63175, Q68EV0, Q6NRS6, Q6P0S3, Q6UX65, Q6ZMB5, Q7K0P4, Q8BHJ6, Q8N682

Diamond homologs: A5D7C9, A6NC51, A9JSP6, B5DFH9, B9EJG8, Q28BP2, Q32PK2, Q3ZC48, Q4V7T3, Q4V7T7, Q6UX65, Q8C8S3, Q8R218, A7MBB3, Q5BK09, Q6GPL4, Q86TG1, Q91WN2, Q9CR48, Q9DC58, Q9QZE9, Q8N682, Q5EAK8, Q6NRS6

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
DRAM2	“up-regulates quantity by expression”	RAC1	“transcriptional regulation”
DRAM2	“up-regulates quantity by expression”	RHOA	“transcriptional regulation”
DRAM2	“up-regulates quantity by expression”	RHOC	“transcriptional regulation”
DRAM2	“up-regulates quantity by expression”	ROCK1	“transcriptional regulation”
DRAM2	“down-regulates quantity by repression”	RHOB	“transcriptional regulation”
DRAM2	“down-regulates quantity by repression”	TP53	“transcriptional regulation”
DRAM2	“down-regulates quantity by repression”	CDKN1A	“transcriptional regulation”
TP53	“down-regulates quantity by repression”	DRAM2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	10
Uncertain significance	101
Likely benign	71
Benign	6

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074281	NM_001349884.2(DRAM2):c.92dup (p.Thr32fs)	Pathogenic
1322768	NM_001349884.2(DRAM2):c.80dup (p.Tyr27Ter)	Pathogenic
1367200	NM_001349884.2(DRAM2):c.3G>A (p.Met1Ile)	Pathogenic
1369252	NM_001349884.2(DRAM2):c.5G>A (p.Trp2Ter)	Pathogenic
1396222	NM_001349884.2(DRAM2):c.678C>A (p.Tyr226Ter)	Pathogenic
1453413	NM_001349884.2(DRAM2):c.638G>A (p.Trp213Ter)	Pathogenic
1461350	NM_001349884.2(DRAM2):c.642dup (p.Met215fs)	Pathogenic
1486555	NM_001349884.2(DRAM2):c.731T>G (p.Leu244Ter)	Pathogenic
192233	NM_001349884.2(DRAM2):c.140del (p.Gly47fs)	Pathogenic
192234	NM_001349884.2(DRAM2):c.61GCT[1] (p.Ala22del)	Pathogenic
192235	NM_001349884.2(DRAM2):c.79T>C (p.Tyr27His)	Pathogenic
192236	NM_001349884.2(DRAM2):c.217_225del (p.Val73_Tyr75del)	Pathogenic
192237	NM_001349884.2(DRAM2):c.362A>T (p.His121Leu)	Pathogenic
192238	NM_001349884.2(DRAM2):c.131G>A (p.Ser44Asn)	Pathogenic
192239	NM_001349884.2(DRAM2):c.494G>A (p.Trp165Ter)	Pathogenic
1941242	NM_001349884.2(DRAM2):c.296del (p.Gly99fs)	Pathogenic
2972496	NM_001349884.2(DRAM2):c.439C>T (p.Gln147Ter)	Pathogenic
3687980	NM_001349884.2(DRAM2):c.571C>T (p.Gln191Ter)	Pathogenic
3693561	NM_001349884.2(DRAM2):c.618del (p.Met206fs)	Pathogenic
833095	NC_000001.11:g.(?111120496)(111120713_?)del	Pathogenic
856685	NM_001349884.2(DRAM2):c.677dup (p.Tyr226Ter)	Pathogenic
1299331	NM_001349884.2(DRAM2):c.98_99del (p.Leu33fs)	Likely pathogenic
1478004	NM_001349884.2(DRAM2):c.199+1G>A	Likely pathogenic
1518344	NM_001349884.2(DRAM2):c.200-2_211del	Likely pathogenic
2093364	NM_001349884.2(DRAM2):c.601-1G>A	Likely pathogenic
3250335	NM_001349884.2(DRAM2):c.231A>T (p.Gln77His)	Likely pathogenic
3544430	NM_001349884.2(DRAM2):c.314G>T (p.Gly105Val)	Likely pathogenic
369954	NM_001349884.2(DRAM2):c.568G>T (p.Glu190Ter)	Likely pathogenic
3718574	NM_001349884.2(DRAM2):c.518-1G>A	Likely pathogenic
4813321	NM_001349884.2(DRAM2):c.693+2T>A	Likely pathogenic

SpliceAI

1826 predictions. Top by Δscore:

Variant	Effect	Δscore
1:111118799:TCTTA:T	donor_loss	1.0000
1:111118800:CTTA:C	donor_loss	1.0000
1:111118801:TTA:T	donor_loss	1.0000
1:111118802:TACCT:T	donor_loss	1.0000
1:111118803:A:AT	donor_loss	1.0000
1:111118804:C:A	donor_loss	1.0000
1:111119875:A:AC	donor_gain	1.0000
1:111119876:C:CC	donor_gain	1.0000
1:111119955:CAGCA:C	acceptor_gain	1.0000
1:111119958:CA:C	acceptor_gain	1.0000
1:111119960:C:CC	acceptor_gain	1.0000
1:111126295:C:CC	acceptor_gain	1.0000
1:111131419:CTTA:C	donor_loss	1.0000
1:111131420:TTA:T	donor_loss	1.0000
1:111131421:TACC:T	donor_loss	1.0000
1:111131422:ACCT:A	donor_loss	1.0000
1:111131423:C:G	donor_loss	1.0000
1:111131566:TTT:T	acceptor_gain	1.0000
1:111131569:C:CC	acceptor_gain	1.0000
1:111118264:TTTT:T	acceptor_gain	0.9900
1:111118893:TAACC:T	acceptor_gain	0.9900
1:111118896:CC:C	acceptor_gain	0.9900
1:111118897:CC:C	acceptor_gain	0.9900
1:111118902:G:GC	acceptor_gain	0.9900
1:111118905:A:C	acceptor_gain	0.9900
1:111119962:A:C	acceptor_gain	0.9900
1:111126225:A:AC	donor_gain	0.9900
1:111126226:C:CC	donor_gain	0.9900
1:111126293:CA:C	acceptor_gain	0.9900
1:111131422:A:AC	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000091836 (1:111125592 G>A), RS1000100981 (1:111131068 A>T), RS1000436710 (1:111132527 A>C), RS1000439355 (1:111116972 T>G), RS1000534999 (1:111130921 C>T), RS1001054354 (1:111131096 AT>A), RS1001187622 (1:111140247 A>C,G,T), RS1001375926 (1:111123692 T>G), RS1001501050 (1:111124007 T>A,C), RS1001505384 (1:111127705 A>G), RS1001555246 (1:111123544 C>T), RS1001662821 (1:111133779 T>G), RS1001763556 (1:111127282 G>C), RS1001839104 (1:111129139 T>A), RS1001881720 (1:111137168 G>C)

Disease associations

OMIM: gene MIM:613360 | disease phenotypes: MIM:616502, MIM:120970

GenCC curated gene-disease

Disease	Classification	Inheritance
cone-rod dystrophy 21	Strong	Autosomal recessive
cone-rod dystrophy	Supportive	Autosomal dominant

Mondo (4): inherited retinal dystrophy (MONDO:0019118), cone-rod dystrophy 21 (MONDO:0014669), cone-rod dystrophy (MONDO:0015993), retinal disorder (MONDO:0005283)

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

HPO phenotypes

20 total (20 of 20 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:0000551	Color vision defect
HP:0000556	Retinal dystrophy
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0001105	Retinal atrophy
HP:0007401	Macular atrophy
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:0011462	Young adult onset
HP:0012508	Metamorphopsia
HP:0030466	Abnormal full-field electroretinogram

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007998_7	Intraocular pressure	1.000000e-08
GCST90002396_139	Mean reticulocyte volume	4.000000e-14
GCST90002397_768	Mean spheric corpuscular volume	1.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D012164	Retinal Diseases	C11.768
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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	9
methylmercuric chloride	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
sulphoraphene	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Cisplatin	decreases response to substance, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
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]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
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)
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