FRMPD4

FERM and PDZ domain containing 4, the group of PDZ domain containing|FERM domain containing

Basic information

Region (hg38): X:11822423-12724523

Previous symbols: [ "PDZK10", "PDZD10" ]

Links

ENSG00000169933 ∙ NCBI:9758 ∙ OMIM:300838 ∙ HGNC:29007 ∙ Uniprot:Q14CM0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, X-linked 104 (Strong), mode of inheritance: XL
• intellectual disability, X-linked 104 (Strong), mode of inheritance: XL
• intellectual disability, X-linked 104 (Moderate), mode of inheritance: XL
• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• X-linked complex neurodevelopmental disorder (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 104	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	Neurologic	25644381

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FRMPD4 gene.

• not provided (3 variants)
• Intellectual disability, X-linked 104 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FRMPD4 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			6	34	16	56
missense		1	164	30	1	196
nonsense	2	3				5
start loss						0
frameshift	1	6				7
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region			6	3		9
non coding			3	2	5	10
Total	4	12	175	66	22

Variants in FRMPD4

This is a list of pathogenic ClinVar variants found in the FRMPD4 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-11877964-C-T			Uncertain significance (Jan 01, 2024)
X-11878025-A-G			Likely benign (May 01, 2023)
X-12139015-A-G			Uncertain significance (Apr 05, 2022)
X-12494952-C-T			Likely benign (Mar 01, 2023)
X-12498658-CT-C		not specified	Benign (May 28, 2013)
X-12498658-C-CT		not specified	Benign (Aug 08, 2014)
X-12498671-C-A		not specified • FRMPD4-related disorder	Conflicting classifications of pathogenicity (Jul 12, 2024)
X-12498685-G-T			Uncertain significance (Feb 15, 2024)
X-12498688-C-T		Inborn genetic diseases	Likely benign (May 26, 2024)
X-12498700-G-A			Uncertain significance (Mar 29, 2023)
X-12498715-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (May 23, 2024)
X-12498716-G-A			Benign (Dec 31, 2019)
X-12498763-C-T		FRMPD4-related disorder	Likely benign (Dec 01, 2022)
X-12498772-G-A		Inborn genetic diseases	Uncertain significance (Oct 16, 2023)
X-12609725-A-G		Inborn genetic diseases	Uncertain significance (Jun 19, 2024)
X-12609733-G-C		Inborn genetic diseases	Uncertain significance (Dec 13, 2023)
X-12609744-T-A		not specified	Uncertain significance (Oct 16, 2020)
X-12609749-G-A		Inborn genetic diseases	Uncertain significance (Jun 23, 2021)
X-12609755-C-T			Uncertain significance (Jul 24, 2019)
X-12609756-G-A			Uncertain significance (Feb 07, 2019)
X-12609762-A-G			Uncertain significance (Jul 07, 2020)
X-12609775-C-G		Inborn genetic diseases	Uncertain significance (Feb 28, 2019)
X-12609783-C-T		Inborn genetic diseases	Likely benign (May 28, 2024)
X-12609784-G-A		not specified	Likely benign (Aug 30, 2019)
X-12609792-G-A		Inborn genetic diseases	Uncertain significance (Oct 28, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FRMPD4	protein_coding	protein_coding	ENST00000380682	17	586058

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000285	124979	0	1	124980	0.00000400

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.95	414	542	0.764	0.0000443	8659
Missense in Polyphen		106	213.89	0.49558		3430
Synonymous	-1.61	263	232	1.13	0.0000212	2638
Loss of Function	5.54	0	35.7	0.00	0.00000264	658

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)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.000210	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Positive regulator of dendritic spine morphogenesis and density. Required for the maintenance of excitatory synaptic transmission. Binds phosphatidylinositol 4,5-bisphosphate. {ECO:0000269|PubMed:19118189}.
• Disease: DISEASE: Mental retardation, X-linked 104 (MRX104) [MIM:300983]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269|PubMed:25644381}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0975

Intolerance Scores

• loftool: 0.0193
• rvis_EVS: -1.84
• rvis_percentile_EVS: 2.07

Haploinsufficiency Scores

• pHI: 0.245
• hipred: Y
• hipred_score: 0.809
• ghis: 0.620

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.267

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Frmpd4
• 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); 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)

Gene ontology

• Biological process: positive regulation of synapse structural plasticity;postsynaptic actin cytoskeleton organization
• Cellular component: cytoskeleton;postsynaptic density;protein-containing complex;dendritic spine;glutamatergic synapse
• Molecular function: protein binding;phosphatidylinositol-4,5-bisphosphate binding