OPHN1

oligophrenin 1, the group of AH/BAR family Rho GTPase activating proteins

Basic information

Region (hg38): X:67949348-68433913

Previous symbols: [ "MRX60" ]

Links

ENSG00000079482 ∙ NCBI:4983 ∙ OMIM:300127 ∙ HGNC:8148 ∙ Uniprot:O60890 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked intellectual disability-cerebellar hypoplasia syndrome (Definitive), mode of inheritance: XLR
• X-linked intellectual disability-cerebellar hypoplasia syndrome (Strong), mode of inheritance: XL
• X-linked intellectual disability-cerebellar hypoplasia syndrome (Supportive), mode of inheritance: XL
• X-linked intellectual disability-cerebellar hypoplasia syndrome (Strong), mode of inheritance: XL
• X-linked intellectual disability-cerebellar hypoplasia syndrome (Definitive), mode of inheritance: XL
• X-linked intellectual disability-cerebellar hypoplasia syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndromic, Billuart type	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	9582072; 12807966; 16158428; 16221952; 20528889

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OPHN1 gene.

• not provided (250 variants)
• X-linked intellectual disability-cerebellar hypoplasia syndrome (54 variants)
• Inborn genetic diseases (45 variants)
• not specified (32 variants)
• OPHN1-related condition (6 variants)
• 6 conditions (1 variants)
• Abnormality of the nervous system (1 variants)
• Autism spectrum disorder (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OPHN1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				37	2	39
missense		7	121	10	4	142
nonsense	4	1	2			7
start loss						0
frameshift	9	5				14
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	5	10				15
splice region		2	8	8	1	19
non coding			2	28	42	72
Total	18	24	126	75	48

Highest pathogenic variant AF is 0.0000179

Variants in OPHN1

This is a list of pathogenic ClinVar variants found in the OPHN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-68048175-T-C			Benign (Jun 26, 2018)
X-68048432-C-A			Uncertain significance (Feb 14, 2023)
X-68048441-G-A		Inborn genetic diseases • OPHN1-related disorder	Uncertain significance (Apr 12, 2023)
X-68048445-T-A			Uncertain significance (May 25, 2023)
X-68048448-G-T			Likely benign (Jan 30, 2024)
X-68048453-G-A			Uncertain significance (Nov 15, 2019)
X-68048476-G-A			Benign (Jan 21, 2024)
X-68048534-C-A			Benign (Jun 14, 2018)
X-68052289-C-CA			Benign (Aug 10, 2019)
X-68052289-C-CAA			Benign (Aug 10, 2019)
X-68052531-A-T			Likely benign (Nov 08, 2023)
X-68052533-A-C			Likely benign (Nov 08, 2023)
X-68052533-A-G			Likely benign (May 05, 2022)
X-68052552-C-T		Inborn genetic diseases • X-linked intellectual disability-cerebellar hypoplasia syndrome	Uncertain significance (Jan 25, 2024)
X-68052553-G-A		not specified • Inborn genetic diseases • X-linked intellectual disability-cerebellar hypoplasia syndrome • OPHN1-related disorder	Benign/Likely benign (Apr 01, 2024)
X-68052594-C-A			Likely benign (Jun 26, 2017)
X-68052598-C-T			Likely benign (Oct 22, 2023)
X-68052609-C-A			Likely benign (Jul 03, 2023)
X-68053625-T-G			Likely benign (Apr 18, 2022)
X-68053635-C-A		not specified	Benign (Jan 12, 2024)
X-68053649-A-G			Uncertain significance (Sep 01, 2022)
X-68053653-T-C			Conflicting classifications of pathogenicity (Oct 01, 2022)
X-68053654-G-A			Uncertain significance (Dec 08, 2021)
X-68053659-T-A		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
X-68053662-C-T		not specified	Benign/Likely benign (Jan 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OPHN1	protein_coding	protein_coding	ENST00000355520	23	391570

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000151	125665	1	1	125667	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.59	174	300	0.579	0.0000222	5324
Missense in Polyphen		41	110.44	0.37123		1934
Synonymous	0.180	109	111	0.978	0.00000833	1485
Loss of Function	4.86	1	29.5	0.0339	0.00000201	559

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000123	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.0000534	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stimulates GTP hydrolysis of members of the Rho family. Its action on RHOA activity and signaling is implicated in growth and stabilization of dendritic spines, and therefore in synaptic function. Critical for the stabilization of AMPA receptors at postsynaptic sites. Critical for the regulation of synaptic vesicle endocytosis at presynaptic terminals. Required for the localization of NR1D1 to dendrites, can suppress its repressor activity and protect it from proteasomal degradation (By similarity). {ECO:0000250}.
• Pathway: Signal Transduction;Rho GTPase cycle;Signaling by Rho GTPases;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.197

Intolerance Scores

• rvis_EVS: 0.51
• rvis_percentile_EVS: 80.2

Haploinsufficiency Scores

• pHI: 0.155
• hipred: Y
• hipred_score: 0.786
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.759

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ophn1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: substrate-dependent cell migration, cell extension;signal transduction;nervous system development;axon guidance;cerebellar granule cell differentiation;cerebral cortex neuron differentiation;actin cytoskeleton organization;regulation of endocytosis;neuron differentiation;neuron projection development;cell junction assembly;regulation of Rho protein signal transduction;positive regulation of GTPase activity;establishment of epithelial cell apical/basal polarity;synaptic vesicle endocytosis;cell morphogenesis involved in neuron differentiation;regulation of small GTPase mediated signal transduction;regulation of synaptic transmission, glutamatergic;maintenance of postsynaptic specialization structure;regulation of postsynaptic neurotransmitter receptor internalization;negative regulation of proteasomal protein catabolic process
• Cellular component: cytoplasm;cytosol;actin cytoskeleton;cell junction;terminal bouton;dendritic spine;glutamatergic synapse
• Molecular function: actin binding;GTPase activator activity;phospholipid binding;ionotropic glutamate receptor binding