CNNM4

Summary

CNNM4 (cyclin and CBS domain divalent metal cation transport mediator 4, HGNC:105) is a protein-coding gene on chromosome 2q11.2, encoding Metal transporter CNNM4 (Q6P4Q7). Probable metal transporter.

This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play a role in metal ion transport. Mutations in this gene are associated with Jalili syndrome which consists of cone-rod dystrophy and amelogenesis imperfecta.

Source: NCBI Gene 26504 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Jalili syndrome (Definitive, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 609 total — 34 pathogenic, 17 likely-pathogenic (top 5% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 22 tissues, sQTL in 15 (q < 0.05)
• Phenotypes (HPO): 25
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.79 (unconstrained)
• MANE Select transcript: NM_020184

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:105
Approved symbol	CNNM4
Name	cyclin and CBS domain divalent metal cation transport mediator 4
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	SLC70A4, KIAA1592
Ensembl gene	ENSG00000158158
Ensembl biotype	protein_coding
OMIM	607805
Entrez	26504

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000377075

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 2, TSL 4: 1

ENST00000377075, ENST00000482716, ENST00000493384, ENST00000496186, ENST00000930282, ENST00000966765, ENST00001124300, ENST00001145231

RefSeq mRNA: 1 — MANE Select: NM_020184 NM_020184

CCDS: CCDS2024

Canonical transcript exons

ENST00000377075 — 7 exons

Exon	Start	End
ENSE00001037348	96808561	96808742
ENSE00001037357	96809320	96811874
ENSE00001071928	96760902	96762401
ENSE00003478814	96797513	96797647
ENSE00003624061	96799057	96799226
ENSE00003628156	96799552	96799648
ENSE00003650175	96797012	96797155

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 92.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9939 / max 788.0031, expressed in 1759 samples.

Highest expression (Bgee): mucosa of transverse colon, rectum, ileal mucosa, hindlimb stylopod muscle, colonic mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CNNM4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 22 tissues and its splicing (sQTL) in 15 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 37 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	1.5e-58	+1.11	2:96773264:A:T
Skin Sun Exposed Lower leg	sqtl	6.4e-15	+0.48	2:96797792:G:A
Thyroid	sqtl	1.0e-14	+0.56	2:96773264:A:T
Nerve Tibial	sqtl	6.4e-13	+0.51	2:96788968:C:T
Cells EBV-transformed lymphocytes	sqtl	4.5e-12	+0.75	2:96773264:A:T
Skin Sun Exposed Lower leg	eqtl	8.8e-11	+0.24	2:96759824:A:G
Colon Transverse	eqtl	2.3e-09	+0.13	2:96730666:T:C
Testis	eqtl	1.2e-07	+0.18	2:96757889:T:C
Colon Transverse	sqtl	1.5e-07	+0.54	2:96773264:A:T
Whole Blood	eqtl	4.2e-07	+0.12	2:96757889:T:C
Muscle Skeletal	eqtl	6.5e-07	+0.11	2:96730666:T:C
Brain Nucleus accumbens basal ganglia	eqtl	4.1e-06	+1.58	2:96430504:C:T
Brain Cerebellar Hemisphere	eqtl	7.2e-06	+0.26	2:96726970:C:G
Breast Mammary Tissue	sqtl	7.9e-06	+0.42	2:96730666:T:C
Small Intestine Terminal Ileum	sqtl	1.0e-05	+0.76	2:96773264:A:T
Brain Hypothalamus	eqtl	1.3e-04	+1.63	2:96430504:C:T
Brain Cerebellum	eqtl	1.8e-04	+0.26	2:96686672:T:A
Cells Cultured fibroblasts	eqtl	2.2e-04	+0.14	2:96687988:G:A
Spleen	sqtl	3.8e-04	+0.57	2:96773264:A:T
Adipose Visceral Omentum	eqtl	5.7e-04	+0.14	2:96788968:C:T

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
21480	10.8021	1727
21479	0.5484	299
21484	0.2589	58
21478	0.2570	78
21485	0.0687	23
21483	0.0588	24

Top tissues by expression

showing 100 of 259 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	92.61	gold quality
rectum	UBERON:0001052	92.09	gold quality
ileal mucosa	UBERON:0000331	89.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.29	gold quality
colonic mucosa	UBERON:0000317	89.20	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.17	gold quality
transverse colon	UBERON:0001157	86.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.43	gold quality
cerebellar hemisphere	UBERON:0002245	86.21	gold quality
muscle of leg	UBERON:0001383	86.10	gold quality
cerebellar cortex	UBERON:0002129	86.10	gold quality
gastrocnemius	UBERON:0001388	85.80	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.71	silver quality
apex of heart	UBERON:0002098	85.67	gold quality
cerebellum	UBERON:0002037	84.89	gold quality
muscle organ	UBERON:0001630	84.60	gold quality
triceps brachii	UBERON:0001509	84.17	silver quality
right uterine tube	UBERON:0001302	84.14	gold quality
heart left ventricle	UBERON:0002084	83.22	gold quality
cardiac ventricle	UBERON:0002082	82.82	gold quality
gluteal muscle	UBERON:0002000	82.12	silver quality
large intestine	UBERON:0000059	81.94	gold quality
colon	UBERON:0001155	81.94	gold quality
skeletal muscle tissue	UBERON:0001134	81.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.51	gold quality
islet of Langerhans	UBERON:0000006	81.38	gold quality
biceps brachii	UBERON:0001507	81.26	gold quality
cortical plate	UBERON:0005343	80.78	gold quality
intestine	UBERON:0000160	80.68	gold quality
colonic epithelium	UBERON:0000397	80.28	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	80.24	gold quality
muscle tissue	UBERON:0002385	79.89	gold quality
heart	UBERON:0000948	79.83	gold quality
vastus lateralis	UBERON:0001379	79.83	silver quality
right atrium auricular region	UBERON:0006631	79.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.38	gold quality
quadriceps femoris	UBERON:0001377	79.06	silver quality
small intestine Peyer’s patch	UBERON:0003454	78.73	gold quality
adenohypophysis	UBERON:0002196	78.63	gold quality
sural nerve	UBERON:0015488	78.50	gold quality
cardiac atrium	UBERON:0002081	78.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.05	gold quality
pituitary gland	UBERON:0000007	77.45	gold quality
small intestine	UBERON:0002108	77.43	gold quality
pancreatic ductal cell	CL:0002079	77.32	silver quality
granulocyte	CL:0000094	76.96	gold quality
tibial nerve	UBERON:0001323	76.94	gold quality
lower esophagus mucosa	UBERON:0035834	76.85	gold quality
pancreas	UBERON:0001264	76.67	gold quality
ventricular zone	UBERON:0003053	76.41	gold quality
stromal cell of endometrium	CL:0002255	76.28	gold quality
body of stomach	UBERON:0001161	76.22	gold quality
ganglionic eminence	UBERON:0004023	76.21	gold quality
prefrontal cortex	UBERON:0000451	76.14	gold quality
right lobe of thyroid gland	UBERON:0001119	76.12	gold quality
esophagus mucosa	UBERON:0002469	76.08	gold quality
upper lobe of left lung	UBERON:0008952	76.01	gold quality
thyroid gland	UBERON:0002046	75.99	gold quality
skin of leg	UBERON:0001511	75.85	gold quality
left lobe of thyroid gland	UBERON:0001120	75.83	gold quality
body of pancreas	UBERON:0001150	75.68	gold quality
vermiform appendix	UBERON:0001154	75.62	gold quality
minor salivary gland	UBERON:0001830	75.53	gold quality
mucosa of stomach	UBERON:0001199	75.39	gold quality
right frontal lobe	UBERON:0002810	75.15	gold quality
diaphragm	UBERON:0001103	75.12	gold quality
stomach	UBERON:0000945	75.08	gold quality
palpebral conjunctiva	UBERON:0001812	74.79	gold quality
saliva-secreting gland	UBERON:0001044	74.61	gold quality
monocyte	CL:0000576	74.58	gold quality
leukocyte	CL:0000738	74.54	gold quality
metanephros cortex	UBERON:0010533	74.53	gold quality
gall bladder	UBERON:0002110	74.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	74.37	gold quality
skin of abdomen	UBERON:0001416	74.34	gold quality
mononuclear cell	CL:0000842	74.28	gold quality
ectocervix	UBERON:0012249	74.23	gold quality
deltoid	UBERON:0001476	74.00	silver quality
caecum	UBERON:0001153	73.95	gold quality
esophagus	UBERON:0001043	73.86	gold quality
vagina	UBERON:0000996	73.79	gold quality
right ovary	UBERON:0002118	73.71	gold quality
mouth mucosa	UBERON:0003729	73.71	gold quality
right lung	UBERON:0002167	73.66	gold quality
upper lobe of lung	UBERON:0008948	73.66	gold quality
zone of skin	UBERON:0000014	73.40	gold quality
frontal cortex	UBERON:0001870	73.38	gold quality
left ovary	UBERON:0002119	73.29	gold quality
endocervix	UBERON:0000458	73.19	gold quality
neocortex	UBERON:0001950	73.13	gold quality
right testis	UBERON:0004534	72.92	gold quality
anatomical system	UBERON:0000467	72.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	72.76	gold quality
left testis	UBERON:0004533	72.75	gold quality
body of uterus	UBERON:0009853	72.74	gold quality
multicellular organism	UBERON:0000468	72.59	gold quality
material anatomical entity	UBERON:0000465	72.57	gold quality
testis	UBERON:0000473	72.51	gold quality
popliteal artery	UBERON:0002250	72.50	gold quality
smooth muscle tissue	UBERON:0001135	72.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.10

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Retina	tissue	36.0
Rectum	tissue	32.2	high
Colon	tissue	30.4	high
Skeletal muscle	tissue	23.2	medium
Tongue	tissue	12.2
Stomach 1	tissue	12.1	high
Heart muscle	tissue	11.1	low
Small intestine	tissue	10.6	high
Nucleus accumbens	tissue	10.2
Fallopian tube	tissue	9.8	medium
Thyroid gland	tissue	8.9	low
Pituitary gland	tissue	8.8
Cerebellum	tissue	8.6	high
Hippocampus	tissue	8.6	high
Locus coeruleus	tissue	8.1
Postcentral gyrus	tissue	7.9
Lung	tissue	7.6	low
Testis	tissue	7.0	high
Skin 1	tissue	6.7	low
Breast	tissue	6.6	medium
Salivary gland	tissue	6.4	low
Vagina	tissue	6.2	not detected
Choroid plexus	tissue	6.1
Parathyroid gland	tissue	6.0	not detected
Duodenum	tissue	5.8	medium
Corpus callosum	tissue	5.8
Hippocampal formation	tissue	5.8
Appendix	tissue	5.7	high
Placenta	tissue	5.4	medium
Olfactory bulb	tissue	5.4
Esophagus	tissue	5.3	not detected
Cerebral cortex	tissue	5.2	high
Pancreas	tissue	5.2	not detected
Caudate putamen	tissue	5.2
Somatosensory cortex	tissue	5.2
Insular cortex	tissue	5.2
Urinary bladder	tissue	5.1	medium
Prostate	tissue	5.1	medium
Cervix	tissue	5.0	medium
Spinal cord	tissue	5.0
Entorhinal cortex	tissue	5.0
Ventral forebrain	tissue	5.0
Occipital cortex	tissue	5.0
Prefrontal cortex	tissue	4.9
Motor cortex	tissue	4.9
Seminal vesicle	tissue	4.8	medium
Basal ganglia	tissue	4.8	high
Amygdala	tissue	4.7
Bone marrow	tissue	4.7	not detected
Putamen	tissue	4.6
Tonsil	tissue	4.6	low
Retrosplenial and cingulate cortex	tissue	4.6
Temporal cortex	tissue	4.6
Septum	tissue	4.5
Retrosplenial cortex	tissue	4.5
Smooth muscle	tissue	4.4	not detected
Epididymis	tissue	4.4	medium
Midbrain	tissue	4.4
Medulla oblongata	tissue	4.4
Superior colliculi	tissue	4.4

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Flocculonodular lobe (23.6), Vermis (22.4), Cerebellar cortex (22.2), Claustrum (14.4), Parieto-temporal junction (white matter) (11.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CNNM4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 158 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-548AJ-5P	99.78	71.12	3085

Functional genomics

gnomAD constraint: pLI 2.44e-06, LOEUF 0.794, missense Z 2.96 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000377075 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:96,761,000–96,797,039	473 / 624.6	0.76	no
2:96,797,040–96,797,087	4 / 21.0	0.19	yes (p 2.0e-04)
2:96,797,088–96,809,514	307 / 376.3	0.82	no
ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 22)

• Identification of CNNM4 as the causative gene for Jalili syndrome, characterized by autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. (PMID:19200525)
• Since CNNM4 is implicated in metal ion transport, cone-rod dystrophy and amelogenesis imperfecta may originate from abnormal ion homeostasis. (PMID:19200527)
• This work describes the purification and preliminary crystallographic analysis of the CBS-pair regulatory domain of the human ancient domain protein 4 (ACDP4), also known as CNNM4. (PMID:21393841)
• Our case shows a unique combination of NF1 and Jalili syndrome; clinical examination, but also of molecular genetic analysis, which together provide a precise diagnosis. (PMID:21728811)
• The c.1312 dupC mutation of CNNM4 leads to a premature termination of amelogenesis resulting in thin, incompletely mineralized enamel, whereas in dentin, only mineralization is disturbed. (PMID:24194943)
• These results demonstrate the crucial importance of Mg(2+) extrusion by CNNM4 in organismal and topical regulation of magnesium. (PMID:24339795)
• Data indicate that a mutation in the cystathionine-beta-synthase (CBS) domains of ancient conserved domain protein 4/cyclin M4 CNNM4 completely abrogated their Mg2+ efflux functions. (PMID:24706765)
• these results indicate that CNNM4-dependent Mg(2+) efflux suppresses tumor progression by regulating energy metabolism. (PMID:25347473)
• CNNM4 is sorted to the basolateral membrane by the complementary function of AP-1A and AP-1B (PMID:25449265)
• These results suggest a new role of CNNM4 in sperm Ca(2+) homeostasis. (PMID:27006114)
• We describe three siblings with clinical features of Jalili syndrome with a homozygous missense mutation in exon 4 of CNNM4, c.1781A>G (p.N594S). (PMID:27070327)
• We identified a novel homozygous deleterious mutation in CNNM4 gene which causes Jalili syndrome. (PMID:27419834)
• used Sanger sequencing to analyze a large consanguineous family with three siblings affected with Jalili syndrome, suspected clinically after dental and ophthalmological examination. These patients are carrying a novel homozygous mutation in the splice site acceptor of intron 3 (c.1682-1G > C) in the CNNM4 gene (PMID:28246031)
• Mutational analysis showed in all three brothers a novel likely pathogenic homozygous missense substitution in exon 1 (c.1076T>C, p.(Leu359Pro)) of CNNM4. Both parents were carriers for the variant. (PMID:28586144)
• Results identified linkage at chromosome 2p14-2q14 and found a homozygous mutation in the CNNM4 gene (p.R605X) causing Jalili syndrome. The truncated CNNM4 protein starting at R605 significantly increased the rate of apoptosis, and significantly increased the interaction between CNNM4 and IQCB1. This mutation may cause Jalili syndrome by a nonsense-mediated decay mechanism, affecting the function of IQCB1 and apoptosis. (PMID:29322253)
• Jalili Syndrome is a rare cone-rod dystrophy (CORD) and amelogenesis imperfecta (AI), We have further characterized its ocular phenotype, including describing SD-OCT, FAF, and electrophysiological features; and report several novel disease-causing sequence variants. (PMID:29421294)
• Here, we report the 2 first families with Jalili Syndrome in Brazil. Molecular analysis of the first family identified a previously described homozygous mutation (p.Leu324Pro) in exon 1 of CNNM4 gene. In the second family, affected patients demonstrated a compound heterozygous mutation in CNNM4, the p.Leu324Pro and the novel nonsense mutation p.Tyr581*. (PMID:29421602)
• The novel identified variant in CNNM4 is the first report from the Pakistani population. Sequence analysis of CNNM4 revealed a novel missense variant (c.1220G>T, p.Arg407Leu) in exon-1 encoding cystathionine-beta-synthase (CBS) domain. (PMID:31347285)
• Expanding the genotypic spectrum of Jalili syndrome: Novel CNNM4 variants and uniparental isodisomy in a north American patient cohort. (PMID:32022389)
• CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells. (PMID:34928937)
• Novel CNNM4 variant and clinical features of Jalili syndrome. (PMID:36354001)
• Dimerization of the CNNM extracellular domain. (PMID:38149326)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnnm4b	ENSDARG00000074309
danio_rerio	cnnm4a	ENSDARG00000102380
danio_rerio	cnnm4b	ENSDARG00000103737
		ENSDARG00000114841
mus_musculus	Cnnm4	ENSMUSG00000037408
rattus_norvegicus	Cnnm4	ENSRNOG00000015886
drosophila_melanogaster	uex	FBGN0262124
caenorhabditis_elegans		WBGENE00011260
caenorhabditis_elegans		WBGENE00016343
caenorhabditis_elegans		WBGENE00016879

Paralogs (3): CNNM1 (ENSG00000119946), CNNM2 (ENSG00000148842), CNNM3 (ENSG00000168763)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2151060) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating magnesium level	2
abnormal tooth morphology	1
abnormal enamel morphology	1
abnormal feces composition	1
increased systemic arterial diastolic blood pressure	1
increased systemic arterial systolic blood pressure	1
increased susceptibility to induced morbidity/mortality	1
decreased urine magnesium level	1
abnormal tooth color	1
abnormal enamel mineralization	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2	P0A2L3	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Typhi	P0A2L4	100.0%	Diamond
Escherichia coli K-12	P0AE78	100.0%	Diamond
Escherichia coli CFT073	P0AE79	100.0%	Diamond
Escherichia coli O157:H7	P0AE80	100.0%	Diamond
Shigella flexneri	P0AE81	100.0%	Diamond
Arabidopsis thaliana	Q8VZI2	87.1%	Diamond
Buchnera aphidicola str. Sg (Schizaphis graminum)	Q8K9C0	84.8%	Diamond
Haemophilus influenzae Rd KW20	Q57368	81.3%	Diamond
Pasteurella multocida subsp. multocida str. Pm70	Q9CM13	81.3%	Diamond
Xenopus tropicalis	A0JPA0	66.1%	Diamond
Schizosaccharomyces pombe 972h-	Q9USJ3	56.7%	Diamond
Saccharomyces cerevisiae S288C	Q12296	56.6%	Diamond
Brachyspira hyodysenteriae	Q54318	39.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CNNM3-DT	ncRNA	100506036
CNNM3	protein-coding	26505
LMAN2L	protein-coding	81562
FER1L5	protein-coding	90342
MIR3127	ncRNA	100422928
ANKRD23	protein-coding	200539
ANKRD39	protein-coding	51239
ARID5A	protein-coding	10865
KANSL3	protein-coding	55683

Protein

Protein identifiers

Metal transporter CNNM4 — Q6P4Q7 (reviewed: Q6P4Q7)

Alternative names: Ancient conserved domain-containing protein 4, Cyclin-M4

All UniProt accessions (1): Q6P4Q7

UniProt curated annotations — full annotation on UniProt →

Function. Probable metal transporter. The interaction with the metal ion chaperone COX11 suggests that it may play a role in sensory neuron functions. May play a role in biomineralization and retinal function.

Subunit / interactions. Interacts with COX11.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed. Highly expressed in heart.

Disease relevance. Jalili syndrome (JALIS) [MIM:217080] A syndrome characterized by the association of cone-rod dystrophy and amelogenesis imperfecta. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Shares weak sequence similarity with the cyclin family, explaining its name. However, it has no cyclin-like function in vivo.

Similarity. Belongs to the ACDP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P4Q7-1	1	yes
Q6P4Q7-2	2

RefSeq proteins (1): NP_064569* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000595	cNMP-bd_dom	Domain
IPR000644	CBS_dom	Domain
IPR002550	CNNM	Domain
IPR014710	PpnP-like_jellyroll	Homologous_superfamily
IPR018490	cNMP-bd_dom_sf	Homologous_superfamily
IPR044751	Ion_transp-like_CBS	Domain
IPR045095	ACDP	Family
IPR046342	CBS_dom_sf	Homologous_superfamily
IPR057492	Ig_CNNM1/2/4_N	Domain

Pfam: PF00571, PF01595, PF25511, PF25562

Enzyme classification (BRENDA)

• EC 7.2.2.14 — P-type Mg2+ transporter (BRENDA: 30 organisms, 43 substrates, 51 inhibitors, 23 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MG2+	0.006–0.05	8
NI2+	0.002–0.4	5
ATP	1.5–2.8	2
CO2+	0.04–0.08	2
MG2+[SIDE 1]	0.01–0.015	2

UniProt features (27 total): sequence variant 6, topological domain 5, domain 3, modified residue 3, transmembrane region 3, glycosylation site 2, splice variant 2, chain 1, sequence conflict 1, intramembrane region 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
9Y9D	Cryo-EM structure of wild-type human CNNM4 tetramer with Magnesium and MgATP in …	ELECTRON MICROSCOPY	3.48
11GQ	Cryo-EM structure of human CNNM4(E284A) tetramer with Magnesium and MgATP in …	ELECTRON MICROSCOPY	3.54
9Y9F	Cryo-EM structure of human CNNM4(D262C) tetramer with Magnesium and MgATP in occluded …	ELECTRON MICROSCOPY	3.69
6G52	CRYSTAL STRUCTURE OF THE CNMP BINDING DOMAIN OF THE MAGNESIUM TRANSPORTER CNNM4	X-RAY DIFFRACTION	3.69
6RS2	Structure of the Bateman module of human CNNM4.	X-RAY DIFFRACTION	3.69
9Y9G	Cryo-EM structure of human CNNM4(K113A/R140A/R141A) tetramer with Magnesium and MgATP in …	ELECTRON MICROSCOPY	3.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P4Q7-F1	77.20	0.36

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins, Disease related genes, Potential drug targets, Human disease related genes, Eye disease

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): actin filaments; plasma membrane

Antibody reliability (HPA): IH enhanced · IF uncertain

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 (3)

Type	Positions
Phosphoserine	660, 664, 770

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	85, 122

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 201 (showing top): PEREZ_TP63_TARGETS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, MODULE_493, GOBP_TOOTH_MINERALIZATION, GOBP_MAGNESIUM_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_ENAMEL_MINERALIZATION, AML_Q6, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_AMELOGENESIS, PEREZ_TP53_AND_TP63_TARGETS, RYTTCCTG_ETS2_B, GOBP_SENSORY_PERCEPTION, GOBP_MONOATOMIC_ION_HOMEOSTASIS

GO Biological Process (8): visual perception (GO:0007601), magnesium ion homeostasis (GO:0010960), magnesium ion transport (GO:0015693), intracellular monoatomic cation homeostasis (GO:0030003), biomineral tissue development (GO:0031214), monoatomic ion transport (GO:0006811), sodium ion transmembrane transport (GO:0035725), magnesium ion transmembrane transport (GO:1903830)

GO Molecular Function (3): sodium ion transmembrane transporter activity (GO:0015081), magnesium ion transmembrane transporter activity (GO:0015095), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), protein-containing complex (GO:0032991)

GO top-level categories

20 GO namespaces:

Category	Terms
monoatomic cation homeostasis	2
monoatomic cation transmembrane transport	2
metal ion transmembrane transporter activity	2
sensory perception of light stimulus	1
inorganic ion homeostasis	1
metal ion transport	1
intracellular monoatomic ion homeostasis	1
tissue development	1
animal organ development	1
transport	1
sodium ion transport	1
magnesium ion transport	1
sodium ion transmembrane transport	1
magnesium ion transmembrane transport	1
binding	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
cellular_component	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
intracellular monoatomic cation homeostasis	BP	direct assay
plasma membrane	CC	direct assay
protein-containing complex	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 980 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNNM4	COX11	Q9Y6N1	760
CNNM4	MMP20	O60882	741
CNNM4	KLK4	Q9Y5K2	714
CNNM4	MMP25	Q9NPA2	686
CNNM4	TRPM6	Q9BX84	676
CNNM4	SLC41A1	Q8IVJ1	655
CNNM4	CNGA3	Q16281	619
CNNM4	TRPM7	Q96QT4	594
CNNM4	FAM20A	Q96MK3	510
CNNM4	ARL15	Q9NXU5	495
CNNM4	ENAM	Q9NRM1	494
CNNM4	WDR72	Q3MJ13	475
CNNM4	ROGDI	Q9GZN7	466
CNNM4	ODAPH	Q17RF5	465
CNNM4	CERKL	Q49MI3	462

IntAct

Human interaction partners of CNNM4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
PTP4A1	association	0.740	1
PTP4A2	association	0.740	1
KLK14	association	0.350	1
IQCB1	physical association	0.000	1

BioGRID (108 interactions; top human partners by supporting records): PTP4A2 (Affinity Capture-MS; 8 records), PTP4A1 (Affinity Capture-MS; 6 records), LRRC39 (Affinity Capture-MS; 3 records), ARL15 (Affinity Capture-MS; 2 records), TMPRSS4 (Affinity Capture-MS; 2 records), UNC93B1 (Affinity Capture-MS; 2 records), AGK (Affinity Capture-MS), ARMC6 (Affinity Capture-MS), ATP7B (Co-fractionation), B4GAT1 (Affinity Capture-MS), BTNL2 (Affinity Capture-MS), C11orf52 (Proximity Label-MS), CCNF (Affinity Capture-MS), CDC123 (Affinity Capture-MS), CDKN1A (Positive Genetic)

Disease & clinical

Genetic variants

Variant evidence for CNNM4: 609 ClinVar records (51 pathogenic / likely pathogenic); 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	17
Uncertain significance	301
Likely benign	196
Benign	17

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 51 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2850	NM_020184.4(CNNM4):c.1690C>T (p.Gln564Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
434794	NM_020184.4(CNNM4):c.1555C>T (p.Arg519Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
2084124	NM_020184.4(CNNM4):c.1813C>T (p.Arg605Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
867091	NM_020184.4(CNNM4):c.613_621delinsA (p.Gly205fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
518456	NM_020184.4(CNNM4):c.1743C>G (p.Tyr581Ter)	Pathogenic	criteria provided, single submitter	1
801734	NM_020184.4(CNNM4):c.1547-1G>A	Pathogenic	criteria provided, single submitter	1
872329	NM_020184.4(CNNM4):c.1296del (p.Asp433fs)	Pathogenic	criteria provided, single submitter	1
959349	NM_020184.4(CNNM4):c.280del (p.Thr94fs)	Pathogenic	criteria provided, single submitter	1
1054444	NM_020184.4(CNNM4):c.2130+1G>A	Pathogenic	criteria provided, single submitter	1
1069696	NM_020184.4(CNNM4):c.279del (p.Phe93fs)	Pathogenic	criteria provided, single submitter	1
1070169	NM_020184.4(CNNM4):c.620_621del (p.Met207fs)	Pathogenic	criteria provided, single submitter	1
1342702	NM_020184.4(CNNM4):c.1475G>A (p.Gly492Asp)	Pathogenic	criteria provided, single submitter	1
1440136	NM_020184.4(CNNM4):c.2148C>A (p.Tyr716Ter)	Pathogenic	criteria provided, single submitter	1
1443458	NM_020184.4(CNNM4):c.154dup (p.Ala52fs)	Pathogenic	criteria provided, single submitter	1
1450679	NM_020184.4(CNNM4):c.750del (p.Asn250fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CNNM4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 869):

Position(s)	Effect	Δscore	Sites
2:96762402–96762403	donor_loss	1.0000	5
2:96797010	acceptor_loss	1.0000	2
2:96797011	acceptor_gain	1.0000
2:96797156–96797157	donor_loss	1.0000	4
2:96797507	acceptor_gain	1.0000
2:96797511–96797512	acceptor_loss	1.0000	5
2:96799055–96799056	acceptor_loss	1.0000	6
2:96799227–96799228	donor_loss	1.0000	5
2:96799550–96799551	acceptor_loss	1.0000	6
2:96799649–96799650	donor_loss	1.0000	3

AlphaMissense

2,449 missense substitutions predicted likely pathogenic (of 5,084 scored), across 536 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M401	9	0.867	0.989
H471	8	0.999	1.000
D510	8	0.999	1.000
D498	8	0.998	1.000
D426	8	0.997	1.000
D513	8	0.997	0.999
F465	8	0.996	1.000
D485	8	0.996	0.999
F636	8	0.994	1.000
D434	8	0.992	0.998
F429	8	0.990	0.999
D431	8	0.989	0.998
F565	8	0.988	1.000
D697	8	0.986	0.997
F535	8	0.984	0.999
F631	8	0.983	1.000
N254	8	0.982	0.999
F394	8	0.980	1.000
F199	8	0.978	0.996
F93	8	0.977	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Ovary Serous Cystadenocarcinoma (TCGA)	unfavorable	0.00048
Kidney Chromophobe (TCGA)	unfavorable	0.000612
Lung Adenocarcinoma (validation)	unfavorable	0.000727
Rectum Adenocarcinoma (TCGA)	favorable	0.000958

Disease associations

OMIM: gene MIM:607805 | disease phenotypes: MIM:217080

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Jalili syndrome	Definitive	Autosomal recessive	5

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
Jalili syndrome	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Amelogenesis imperfecta	green
Retinal disorders	green
Structural eye disease	amber

Mondo (2): Jalili syndrome (MONDO:0009007), inherited retinal dystrophy (MONDO:0019118)

Orphanet (2): Jalili syndrome (Orphanet:1873), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

25 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000543	Optic disc pallor
HP:0000548	Cone/cone-rod dystrophy
HP:0000551	Color vision defect
HP:0000575	Scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000670	Carious teeth
HP:0000682	Abnormal dental enamel morphology
HP:0000705	Amelogenesis imperfecta
HP:0003593	Infantile onset
HP:0006286	Yellow-brown discoloration of the teeth
HP:0007401	Macular atrophy
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007803	Monochromacy
HP:0007814	Retinal pigment epithelial mottling
HP:0007843	Attenuation of retinal blood vessels
HP:0008499	High hypermetropia
HP:0011073	Abnormality of dental color
HP:0012043	Pendular nystagmus
HP:0033785	Enamel agenesis

GWAS associations

5 associations:

Study	Trait	p-value
GCST003962_1	Bipolar disorder	3e-10
GCST009600_104	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1e-9
GCST008103_173	Bipolar disorder	4e-9
GCST001241_9	Bipolar disorder	2e-6
GCST006865_1	Bipolar disorder	3e-6

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
C000596385	Jalili syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression	3
Benzo(a)pyrene	increases expression, increases methylation	3
Valproic Acid	affects methylation, increases expression, increases methylation	3
sodium arsenite	increases abundance, increases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression	2
Arsenic Trioxide	affects binding, decreases reaction, decreases response to substance	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
K 7174	increases expression	1
licochalcone B	increases expression	1
Aldehydes	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Phenobarbital	affects expression	1
Quercetin	increases expression	1
Sulindac	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 238 trials:

NCT	Phase	Status	Title
NCT00717080	Phase 4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	Phase 3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	Phase 3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	Phase 3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	Phase 3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	Phase 3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	Phase 3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	Phase 3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	Phase 3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	Phase 3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	Phase 3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	Phase 3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	Phase 3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT07710196	Phase 3	NOT_YET_RECRUITING	A 24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	Phase 2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	Phase 2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	Phase 2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	Phase 2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	Phase 2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	Phase 2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	Phase 2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	Phase 2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	Phase 2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	Phase 2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	Phase 2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	Phase 2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	Phase 2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	Phase 2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	Phase 2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	Phase 2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	Phase 2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	Phase 2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	Phase 2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	Phase 2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	Phase 2	ACTIVE_NOT_RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	Phase 2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	Phase 2	ACTIVE_NOT_RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT07796646	Phase 2	NOT_YET_RECRUITING	Study to Evaluate the Long-Term Safety of Ultevursen in Participants With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT00063765	Phase 1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	Phase 1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	Phase 1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa
NCT01068561	Phase 1	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT01482195	Phase 1	COMPLETED	Trial of Subretinal Injection of (rAAV2-VMD2-hMERTK)
NCT01531348	Phase 1	COMPLETED	Intravitreal Injection of MSCs in Retinitis Pigmentosa
NCT01543906	Phase 1	COMPLETED	Oral QLT091001 in Retinitis Pigmentosa (RP) Subjects With an Autosomal Dominant Mutation in Retinal Pigment Epithelial 65 Protein (RPE65)
NCT01604356	Phase 1	COMPLETED	Acupuncture for the Treatment of Vision Loss Due to Retinitis Pigmentosa
NCT01736059	Phase 1	ACTIVE_NOT_RECRUITING	Clinical Trial of Autologous Intravitreal Bone-marrow CD34+ Stem Cells for Retinopathy
NCT02280135	Phase 1	COMPLETED	Clinical Trial of Intravitreal Injection of Autologous Bone Marrow Stem Cells in Patients With Retinitis Pigmentosa
NCT03063021	Phase 1	COMPLETED	The FIGHT-RP1 Study
NCT03772938	Phase 1	UNKNOWN	Stem Cells Therapy in Degenerative Diseases of the Retina
NCT03944239	Phase 1	ACTIVE_NOT_RECRUITING	Safety and Efficacy of Subretinal Transplantation of Clinical Human Embryonic Stem Cell Derived Retinal Pigment Epitheliums in Treatment of Retinitis Pigmentosa
NCT03999021	Phase 1	ACTIVE_NOT_RECRUITING	FIGHT-RP 1 Extension Study
NCT04284293	Phase 1	ACTIVE_NOT_RECRUITING	CNS10-NPC for the Treatment of RP
NCT04925687	Phase 1	COMPLETED	Phase 1 Study of Intravitreal Autologous CD34+ Stem Cell Therapy for Retinitis Pigmentosa
NCT05147701	Phase 1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT06291935	Phase 1	RECRUITING	Safety and Tolerability of Intravitreal Administration of VG901 in Patients With Retinitis Pigmentosa Due to Mutations in the CNGA1 Gene
NCT06319872	Phase 1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06460844	Phase 1	ACTIVE_NOT_RECRUITING	Study to Evaluate Safety of RTx-015 Injection in Retinitis Pigmentosa or Choroideremia Patients (ENVISION)
NCT06936787	Phase 1	RECRUITING	An Open-label, Dose-ascending Study of IGT001 for Retinitis Pigmentosa
NCT07774975	Phase 1	NOT_YET_RECRUITING	Safety Evaluation Study of Pitavastatin PLGA Nano-particle for Retinitis Pigmentosa