FRMD7

Summary

FRMD7 (FERM domain containing 7, HGNC:8079) is a protein-coding gene on chromosome Xq26.2, encoding FERM domain-containing protein 7 (Q6ZUT3). Plays a role in neurite development, may be through the activation of the GTPase RAC1. It is haploinsufficient (ClinGen: sufficient evidence).

Predicted to be involved in regulation of neuron projection development. Predicted to act upstream of or within negative regulation of stress fiber assembly; positive regulation of lamellipodium assembly; and positive regulation of small GTPase mediated signal transduction. Located in cytosol; nucleoplasm; and plasma membrane. Implicated in congenital nystagmus 1.

Source: NCBI Gene 90167 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nystagmus 1, congenital, X-linked (Definitive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 529 total — 45 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 7
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_194277

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8079
Approved symbol	FRMD7
Name	FERM domain containing 7
Location	Xq26.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ43346
Ensembl gene	ENSG00000165694
Ensembl biotype	protein_coding
OMIM	300628
Entrez	90167

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000298542, ENST00000370879, ENST00000464296, ENST00000687717

RefSeq mRNA: 2 — MANE Select: NM_194277 NM_001306193, NM_194277

CCDS: CCDS35397, CCDS78504

Canonical transcript exons

ENST00000298542 — 12 exons

Exon	Start	End
ENSE00001095572	132084490	132084585
ENSE00001095575	132082363	132082526
ENSE00001095576	132085581	132085728
ENSE00001095577	132085920	132086034
ENSE00001215459	132080006	132080081
ENSE00001215464	132080198	132080266
ENSE00001215500	132076990	132078966
ENSE00001215507	132094042	132094139
ENSE00001293487	132097266	132097344
ENSE00001304319	132100612	132100716
ENSE00001323090	132099468	132099510
ENSE00001390580	132127788	132128020

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 77.31.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	77.31	gold quality
tendon	UBERON:0000043	64.84	gold quality
cartilage tissue	UBERON:0002418	64.69	gold quality
body of uterus	UBERON:0009853	64.14	gold quality
adult mammalian kidney	UBERON:0000082	62.62	gold quality
myocardium	UBERON:0002349	62.59	gold quality
seminal vesicle	UBERON:0000998	61.53	gold quality
cauda epididymis	UBERON:0004360	61.39	silver quality
nasal cavity epithelium	UBERON:0005384	61.32	gold quality
esophagus squamous epithelium	UBERON:0006920	61.15	gold quality
vena cava	UBERON:0004087	60.25	gold quality
myometrium	UBERON:0001296	59.35	gold quality
corpus epididymis	UBERON:0004359	58.98	gold quality
caput epididymis	UBERON:0004358	58.44	gold quality
kidney	UBERON:0002113	58.01	gold quality
smooth muscle tissue	UBERON:0001135	56.06	gold quality
deltoid	UBERON:0001476	56.05	gold quality
tibia	UBERON:0000979	55.92	gold quality
biceps brachii	UBERON:0001507	55.82	gold quality
layer of synovial tissue	UBERON:0007616	55.65	silver quality
superficial temporal artery	UBERON:0001614	55.64	gold quality
synovial joint	UBERON:0002217	54.92	silver quality
middle temporal gyrus	UBERON:0002771	54.24	gold quality
mucosa of sigmoid colon	UBERON:0004993	54.24	gold quality
oral cavity	UBERON:0000167	54.14	gold quality
skin of hip	UBERON:0001554	53.88	silver quality
ascending aorta	UBERON:0001496	53.84	gold quality
thoracic aorta	UBERON:0001515	53.60	gold quality
quadriceps femoris	UBERON:0001377	53.02	gold quality
vastus lateralis	UBERON:0001379	52.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting FRMD7, 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-6077	99.99	68.04	2299
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-452-3P	99.01	66.25	1241

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• X-linked recessive congenital motor nystagmus mapped to a region overlapped with that for X-linkaged dominant form. (PMID:16240070)
• Restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability. (PMID:17013395)
• report of five novel mutations in FRMD7 and confirm the role of this gene in the pathogenesis of X-linked congenital nystagmus (PMID:17397053)
• These results provide additional evidence for mutations in FRMD7 as a common cause of X-linked congenital motor nystagmus and expand its mutation spectrum. (PMID:17768376)
• We demonstrate that phenotypic variation of nystagmus occurs in families with FRMD7 mutations (PMID:17846367)
• Mutation screening in the FRMD7 gene identified two novel missense mutations (c.781C>G and c.886G>C) and one reported nonsense mutation (c.1003C>T). (PMID:17893669)
• A novel p.R229G missense mutation in the FRMD7 gene causes the NYS phenotype, and skewed X inactivation influences the manifestation of the disease in X linked NYS females. (PMID:17962394)
• The c.425T>G change is predicted to result in the missense substitution of the leucine at codon 142 for an arginine (p.L142R), and supports a causative role for FRMD7 mutations in the pathogenesis of X-linked idiopathic infantile nystagmus. (PMID:18087240)
• Sequencing FRMD7 revealed a G>T transversion (c.812G>T) in exon 9, which caused a conservative substitution of Cys to Phe at codon 271 (p.C271F). (PMID:18246032)
• The mutation of G990T of the FRMD7 gene is the underlying molecular pathogenesis for a family with congenital nystagmus. (PMID:18247295)
• This is first report that five kinds of FRMD7 gene mutation types occurred in Chinese families with Infantile nystagmus (IN), which further support that FRMD7 gene mutations are the underlying pathogenesis of the molecular mechanism for IN. (PMID:18431453)
• identified a novel frameshift mutation (c.1274-1275delTG) in the FRMD7 gene in six X-linked idiopathic congenital nystagmus pedigrees in China (PMID:19072571)
• FRMD7 expression is spatially and temporally regulated in human and mouse brain during embryonic and fetal development. (PMID:19892780)
• Here we show for the first time that large intragenic deletions of FRMD7 can also cause this form of nystagmus. (PMID:20450309)
• Differences in nystagmus characteristics associated with albinism and those associated with FRMD7 mutations leading to idiopathic infantile nystagmus are described for the first-time (PMID:21220551)
• This study showed that mutations in FRMD7 can cause idiopathic infantile periodic alternating nystagmus and may affect neuronal circuits that have been implicated in acquired forms. (PMID:21303855)
• identified a novel mutation, c. 623A>G (p. H208R) in the FRMD7 gene, in a Han Chinese family with infantile nystagmus (PMID:21365021)
• FRMD7 may play an important role in the brainstem in the early stages of development of the human fetal brain, and provides clues for the mechanism of mutation FRMD7, which may be involved in influencing F-actin dynamics. (PMID:21386928)
• Clinicians can use the OKN drum to assess obligate female carriers in a family suspected of having X-linked nystagmus. (PMID:21746984)
• A previously unreported 4 base-pair deletion in the FRMD7 gene (c.1486-1489 del. TTTT) that causes X-linked idiopathic congenital nystagmus has been identified in a Chinese family. (PMID:22065930)
• A novel splice variant of FRMD7 (FRMD7-S) with a shortened exon 4 relative to the original form of FRMD7 (FRMD7-FL) was identified from the cDNA of the human NT2 cell line and mouse fetal brain. (PMID:22128244)
• A novel splicing mutation, (c.163-1 G>T), was detected in the region preceding exon 3 of FRMD7 in a Chinese family patients with X-linked congenital nystagmus. (PMID:22262942)
• A novel missense mutation, c.A917G, was found in family members with congenital nystagmus. (PMID:22490987)
• a model whereby CASK recruits FRMD7 to the plasma membrane to promote neurite outgrowth during development of the oculomotor neural network and that defects in this interaction result in nystagmus. (PMID:23406872)
• Our results expand the spectrum of FRMD7 mutations in association with XLICN, and further confirm that the mutations of FRMD7 are the underlying molecular mechanism for XLICN. (PMID:23733424)
• the identified FRMD7 mutant influences GTPase Rac1 signaling, which regulates neurite development. (PMID:23946638)
• FERM domain containing protein 7 interacts with the Rho GDP dissociation inhibitor and specifically activates Rac1 signaling. (PMID:23967341)
• this study adds a novel mutation (p.I240T) to the existing spectrum of FRMD7 mutations with Congenital, X-Linked Nystagmus. (PMID:24169426)
• we report three novel mutations in FRMD7 in three independent families with XLICN, and provide molecular insights for future XLICN diagnosis and treatment. (PMID:24434814)
• A nonsense mutation (R335X) in the FRMD7 gene was identified in 4 male patients and an asymptomatic female member. (PMID:24513357)
• Abnormal retinal development is associated with FRMD7 mutations. (PMID:24688117)
• We investigated the role of mutations and copy number variations (CNV) of FRMD7 and GPR143 in the molecular pathogenesis of IIN in 49 unrelated Belgian probands. (PMID:25678693)
• a novel mutation c.556A>G (p.M186V) in the gene FRMD7 causes X-linked idiopathic congenital nystagmus in a North Indian family (PMID:25916882)
• We also demonstrated abnormal developments of afferent system in patients with FRMD7 mutations using optical coherence tomography, which may help to understand the etiological factor in development of nystagmus (PMID:26268155)
• Our findings provide further insights into FRMD7 mutations, which could be helpful for future genetic diagnosis and genetic counselling of Chinese patients with nystagmus. (PMID:27036142)
• infantile nystagmus syndrome with FRMD7 mutations in our cases was caused primarily de novo and missense mutations (PMID:28623544)
• These results enriched the gene mutation spectrum of FRMD7. (PMID:28656292)
• A novel mutation in the FRMD7 gene causing idiopathic congenital nystagmus was identified G to T transition (c.886G>T) in exon 9 that resulted in the conservative substitution of a glycine to a cysteine at codon 296. (PMID:30015830)
• We identified five FRMD7 mutations in 35% of our infantile nystagmus syndrome cohort, expanding its mutational spectrum. The missense mutation c.875T>C may be a common mutation arisen from the founder effect in Korea. (PMID:30025138)
• The FERM domain-containing protein 7 (FRMD7) mutation was confirmed in all the affected individuals but was not detected in unaffected family members. (PMID:30576400)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	frmd7	ENSDARG00000068958
danio_rerio	FRMD7	ENSDARG00000070495
mus_musculus	Frmd7	ENSMUSG00000036131
rattus_norvegicus	Frmd7	ENSRNOG00000024762
caenorhabditis_elegans		WBGENE00001366
caenorhabditis_elegans		WBGENE00001490

Paralogs (10): FARP2 (ENSG00000006607), FGD1 (ENSG00000102302), FGD3 (ENSG00000127084), ARHGEF39 (ENSG00000137135), FGD4 (ENSG00000139132), FGD2 (ENSG00000146192), FARP1 (ENSG00000152767), FGD5 (ENSG00000154783), FGD6 (ENSG00000180263), ECT2L (ENSG00000203734)

Protein

Protein identifiers

FERM domain-containing protein 7 — Q6ZUT3 (reviewed: Q6ZUT3)

All UniProt accessions (2): Q6ZUT3, X6R7S7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in neurite development, may be through the activation of the GTPase RAC1. Plays a role in the control of eye movement and gaze stability.

Subcellular location. Cell projection. Neuron projection. Growth cone.

Tissue specificity. Expressed in liver, kidney, pancreas and at low levels in brain and heart. Expressed in embryonic brain and developing neural retina.

Disease relevance. Nystagmus 1, congenital, X-linked (NYS1) [MIM:310700] A form of nystagmus, a condition defined as conjugated, spontaneous and involuntary ocular oscillations that appear at birth or during the first three months of life. Other associated features may include mildly decreased visual acuity, strabismus, astigmatism, and occasionally head nodding. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May play a role during neuronal differentiation and development. Shares a similar tissue distribution, co-localize with, and interact with isoform 1 in NT2 cells.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZUT3-1	1	yes
Q6ZUT3-2	2, S

RefSeq proteins (2): NP_001293122, NP_919253* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR014847	FA	Domain
IPR018979	FERM_N	Domain
IPR018980	FERM_PH-like_C	Domain
IPR019747	FERM_CS	Conserved_site
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035963	FERM_2	Homologous_superfamily
IPR041788	FARP1/FARP2/FRMD7_FERM_C	Domain
IPR051835	RAC1-GEF	Family

Pfam: PF00373, PF08736, PF09379, PF09380

UniProt features (32 total): sequence variant 28, chain 1, domain 1, coiled-coil region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZUT3-F1	62.31	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_LAMELLIPODIUM_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_BUNDLE_ASSEMBLY, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_LAMELLIPODIUM_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BUNDLE_ASSEMBLY

GO Biological Process (5): nervous system development (GO:0007399), positive regulation of lamellipodium assembly (GO:0010592), regulation of neuron projection development (GO:0010975), positive regulation of small GTPase mediated signal transduction (GO:0051057), negative regulation of stress fiber assembly (GO:0051497)

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

GO Cellular Component (9): obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), growth cone (GO:0030426), neuron projection (GO:0043005), neuronal cell body (GO:0043025), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
system development	1
regulation of lamellipodium assembly	1
lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1
neuron projection development	1
regulation of plasma membrane bounded cell projection organization	1
small GTPase-mediated signal transduction	1
regulation of small GTPase mediated signal transduction	1
positive regulation of intracellular signal transduction	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
site of polarized growth	1
distal axon	1
plasma membrane bounded cell projection	1
somatodendritic compartment	1
cell body	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FRMD7	GPR143	P51810	923
FRMD7	CASK	O14936	897
FRMD7	NYX	Q9GZU5	790
FRMD7	OPN1LW	P04000	767
FRMD7	SLC38A8	A6NNN8	645
FRMD7	HPS5	Q9UPZ3	626
FRMD7	RP1L1	Q8IWN7	492
FRMD7	CRYBB3	P26998	491
FRMD7	SLC25A14	O95258	468
FRMD7	PTPRU	P78399	467
FRMD7	WDR49	Q8IV35	465
FRMD7	SLC25A43	Q8WUT9	456
FRMD7	PTPRO	Q16827	456
FRMD7	RAP2C	Q9Y3L5	454
FRMD7	PLEKHH3	Q7Z736	453

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CLNS1A	FRMD7	psi-mi:“MI:0915”(physical association)	0.560
FRMD7	CLNS1A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): CASK (Affinity Capture-MS), FRMD7 (Proximity Label-MS), FRMD7 (Two-hybrid)

ESM2 similar proteins: A2AD83, A4Q9F0, A6QP06, A7KAX9, B2RYE5, B4K6T8, F7E540, G5EEW9, O00443, O13839, O43283, O96838, P11171, P11434, P48193, Q12923, Q14693, Q22744, Q3V0G7, Q5FVG2, Q5R8N8, Q5R8X7, Q5RAY1, Q61194, Q64512, Q6DTM3, Q6GPD0, Q6Q7P4, Q6ZT98, Q6ZUT3, Q811P8, Q8BGS1, Q8BPQ7, Q8CHB8, Q8K3Y6, Q8WYB5, Q91573, Q91ZP3, Q96HH9, Q99PI5

Diamond homologs: A2A2Y4, A2AD83, A2ALK8, B2RYE5, F1LYQ8, F1P065, F8VPU2, O43491, O57457, O70318, O94887, P11171, P11434, P26045, P28191, P29074, P48193, P52963, Q0P4Q4, Q54K81, Q58CU2, Q5FVG2, Q5R803, Q5RAB8, Q6P5H6, Q6Q7P4, Q6ZUT3, Q7Z6J6, Q8BGS1, Q8BHD4, Q91VS8, Q9H329, Q9H4G0, Q9HCM4, Q9HCS5, Q9JMC8, Q9MYU8, Q9N179, Q9V8R9, Q9WTP0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	45
Likely pathogenic	17
Uncertain significance	263
Likely benign	82
Benign	48

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1075004	NM_194277.3(FRMD7):c.706_707del (p.Lys236fs)	Pathogenic
10782	NM_194277.3(FRMD7):c.601C>T (p.Gln201Ter)	Pathogenic
10783	NM_194277.3(FRMD7):c.1003C>T (p.Arg335Ter)	Pathogenic
10784	NM_194277.3(FRMD7):c.205+2T>G	Pathogenic
10785	NM_194277.3(FRMD7):c.252G>A (p.Val84=)	Pathogenic
10786	NM_194277.3(FRMD7):c.70G>A (p.Gly24Arg)	Pathogenic
10787	NM_194277.3(FRMD7):c.38AGA[1] (p.Lys14del)	Pathogenic
10789	NM_194277.3(FRMD7):c.685C>G (p.Arg229Gly)	Pathogenic
10790	NM_194277.3(FRMD7):c.1275_1276del (p.Glu426fs)	Pathogenic
1219261	NM_194277.3(FRMD7):c.47T>C (p.Phe16Ser)	Pathogenic
1343928	NM_194277.3(FRMD7):c.342_343dup (p.Asp115fs)	Pathogenic
1456404	NM_194277.3(FRMD7):c.317T>A (p.Leu106Ter)	Pathogenic
1458988	NM_194277.3(FRMD7):c.1A>G (p.Met1Val)	Pathogenic
1459391	NC_000023.10:g.(?131228050)(131261872_?)del	Pathogenic
1706825	NM_194277.3(FRMD7):c.163-1G>T	Pathogenic
192295	NM_194277.3(FRMD7):c.556A>G (p.Met186Val)	Pathogenic
2017712	NM_194277.3(FRMD7):c.2T>C (p.Met1Thr)	Pathogenic
2097997	NM_194277.3(FRMD7):c.1629del (p.Gln544fs)	Pathogenic
2107948	NM_194277.3(FRMD7):c.1630C>T (p.Gln544Ter)	Pathogenic
2427622	NC_000023.10:g.(?131211900)(131261872_?)del	Pathogenic
2737369	NM_194277.3(FRMD7):c.1493dup (p.Tyr498Ter)	Pathogenic
2737370	NM_194277.3(FRMD7):c.910C>T (p.Arg304Ter)	Pathogenic
2769542	NM_194277.3(FRMD7):c.601del (p.Gln201fs)	Pathogenic
280271	NM_194277.3(FRMD7):c.905+1G>A	Pathogenic
2824989	NM_194277.3(FRMD7):c.561T>A (p.Tyr187Ter)	Pathogenic
29976	NM_194277.3(FRMD7):c.691T>G (p.Leu231Val)	Pathogenic
29977	NM_194277.3(FRMD7):c.812G>A (p.Cys271Tyr)	Pathogenic
29978	NM_194277.3(FRMD7):c.1050+5G>A	Pathogenic
3246949	NC_000023.10:g.(?131211900)(131216574_?)del	Pathogenic
3641510	NM_194277.3(FRMD7):c.339C>A (p.Cys113Ter)	Pathogenic

SpliceAI

1775 predictions. Top by Δscore:

Variant	Effect	Δscore
X:132078985:T:TC	acceptor_gain	1.0000
X:132080264:CCA:C	acceptor_gain	1.0000
X:132080265:CAC:C	acceptor_gain	1.0000
X:132080267:C:CC	acceptor_gain	1.0000
X:132080271:C:CT	acceptor_gain	1.0000
X:132082423:T:TA	donor_gain	1.0000
X:132084482:CTACT:C	donor_loss	1.0000
X:132084483:TACTT:T	donor_loss	1.0000
X:132084484:ACTTA:A	donor_loss	1.0000
X:132084485:CTTA:C	donor_loss	1.0000
X:132084486:TT:T	donor_loss	1.0000
X:132084487:T:TG	donor_loss	1.0000
X:132084488:A:AC	donor_gain	1.0000
X:132084488:ACCA:A	donor_loss	1.0000
X:132084489:C:CC	donor_gain	1.0000
X:132084584:CC:C	acceptor_gain	1.0000
X:132084585:CC:C	acceptor_gain	1.0000
X:132085212:C:CA	donor_gain	1.0000
X:132085222:T:A	donor_gain	1.0000
X:132085597:C:CA	donor_gain	1.0000
X:132085598:C:A	donor_gain	1.0000
X:132085729:C:CC	acceptor_gain	1.0000
X:132094040:A:AC	donor_gain	1.0000
X:132094041:C:CC	donor_gain	1.0000
X:132097346:T:C	acceptor_gain	1.0000
X:132099466:A:AC	donor_gain	1.0000
X:132099467:C:CC	donor_gain	1.0000
X:132100610:A:AC	donor_gain	1.0000
X:132100611:C:CC	donor_gain	1.0000
X:132105175:A:C	acceptor_gain	1.0000

AlphaMissense

4766 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:132082371:G:C	F299L	1.000
X:132082371:G:T	F299L	1.000
X:132082373:A:G	F299L	1.000
X:132082464:C:A	W268C	1.000
X:132082464:C:G	W268C	1.000
X:132082466:A:G	W268R	1.000
X:132082466:A:T	W268R	1.000
X:132082473:C:A	K265N	1.000
X:132082473:C:G	K265N	1.000
X:132082476:G:C	C264W	1.000
X:132084518:A:G	F238S	1.000
X:132084532:A:C	F233L	1.000
X:132084532:A:T	F233L	1.000
X:132084534:A:G	F233L	1.000
X:132084556:C:A	W225C	1.000
X:132084556:C:G	W225C	1.000
X:132084558:A:G	W225R	1.000
X:132084558:A:T	W225R	1.000
X:132082372:A:G	F299S	0.999
X:132082437:G:C	F277L	0.999
X:132082437:G:T	F277L	0.999
X:132082439:A:G	F277L	0.999
X:132082455:A:C	C271W	0.999
X:132082456:C:T	C271Y	0.999
X:132082457:A:G	C271R	0.999
X:132082465:C:G	W268S	0.999
X:132082475:T:C	K265E	0.999
X:132082477:C:T	C264Y	0.999
X:132082501:A:G	F256S	0.999
X:132084529:C:A	K234N	0.999

dbSNP variants (sampled 300 via entrez): RS1000063077 (X:132117616 A>G), RS1000098324 (X:132089431 T>A), RS1000197481 (X:132118598 G>T), RS1000403975 (X:132101695 A>C,T), RS1000428697 (X:132099092 T>C), RS1000699802 (X:132124230 C>A,T), RS1000769640 (X:132090188 C>T), RS1000815868 (X:132096848 A>G), RS1000826587 (X:132081652 C>T), RS1000846253 (X:132116391 G>A), RS1000895677 (X:132103264 C>T), RS1000930456 (X:132106236 T>C), RS1001072936 (X:132115539 G>A), RS1001084293 (X:132115106 G>A), RS1001232890 (X:132124092 G>A,T)

Disease associations

OMIM: gene MIM:300628 | disease phenotypes: MIM:310700, MIM:312870

GenCC curated gene-disease

Disease	Classification	Inheritance
nystagmus 1, congenital, X-linked	Definitive	X-linked

Mondo (3): nystagmus 1, congenital, X-linked (MONDO:0010693), Simpson-Golabi-Behmel syndrome type 1 (MONDO:0020602), inherited retinal dystrophy (MONDO:0019118)

Orphanet (2): Simpson-Golabi-Behmel syndrome (Orphanet:373), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

7 total (8 of 7 shown, HPO-id order):

HPO	Term
HP:0000666	Horizontal nystagmus
HP:0001417	X-linked inheritance
HP:0003593	Infantile onset
HP:0006934	Congenital nystagmus
HP:0007663	Reduced visual acuity
HP:0012043	Pendular nystagmus
HP:0032037	Mildly reduced visual acuity
HP:0000556	Retinal dystrophy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004899_2	Gestational age at birth (maternal effect)	3.000000e-09
GCST006979_843	Heel bone mineral density	3.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005112	gestational age
EFO:0005939	parental genotype effect measurement
EFO:0009270	heel bone mineral density

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
C537853	Nystagmus 1, congenital, X- linked (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
abrine	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Dinitrochlorobenzene	affects binding	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
NCT07502664	Not specified	RECRUITING	Development and Evaluation of Functional Visual Field and Navigation Endpoints in Moderate to Profound Inherited Retinal Disease (DEFINE-IRD)
NCT07529041	Not specified	ENROLLING_BY_INVITATION	Real-time Acoustic Biofeedback for Enhancing Fixation Stability: A Proof-of-concept Study to Improve Ophthalmic Imaging Diagnostic Quality