SYP

synaptophysin, the group of Synaptophysins|MARVEL domain containing

Basic information

Region (hg38): X:49187815-49200218

Links

ENSG00000102003 ∙ NCBI:6855 ∙ OMIM:313475 ∙ HGNC:11506 ∙ Uniprot:P08247 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, X-linked 96 (Limited), mode of inheritance: XL
• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• intellectual disability, X-linked 96 (Limited), mode of inheritance: XL
• intellectual disability, X-linked 96 (Limited), mode of inheritance: XL
• non-syndromic X-linked intellectual disability (Moderate), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 96	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	19377476

ClinVar

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

• Intellectual disability, X-linked 96 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SYP 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			1	4	3	8
missense			40	5		45
nonsense		1	2			3
start loss		1	1			2
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding			1	1		2
Total	1	4	45	10	3

Variants in SYP

This is a list of pathogenic ClinVar variants found in the SYP 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-49191436-A-T			Uncertain significance (Sep 21, 2015)
X-49191477-C-T			Uncertain significance (Jan 21, 2022)
X-49191481-A-G			Uncertain significance (Jan 17, 2023)
X-49191490-G-T			Uncertain significance (Mar 11, 2024)
X-49191493-C-T			Uncertain significance (Oct 02, 2019)
X-49191497-G-C		Intellectual disability, X-linked 96	Uncertain significance (Mar 29, 2024)
X-49191502-C-T		History of neurodevelopmental disorder • not specified	Conflicting classifications of pathogenicity (Dec 31, 2019)
X-49191510-C-T		not specified	Likely benign (Jul 18, 2013)
X-49191511-C-A		not specified • Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 01, 2022)
X-49191526-C-T			Uncertain significance (Jun 01, 2022)
X-49191546-TAGTC-T		Intellectual disability, X-linked 96	Likely pathogenic (Oct 23, 2020)
X-49191578-G-A		not specified	Uncertain significance (Aug 24, 2017)
X-49191592-C-T		Intellectual disability, X-linked 96	Uncertain significance (Jan 13, 2022)
X-49191593-G-C		Intellectual disability, X-linked 96	Uncertain significance (Jul 20, 2022)
X-49191618-C-T			Uncertain significance (Dec 10, 2023)
X-49191674-C-G			Benign (Jul 20, 2018)
X-49191691-C-T		Inborn genetic diseases	Likely benign (Jun 28, 2024)
X-49191692-G-A			Conflicting classifications of pathogenicity (Dec 31, 2019)
X-49191695-C-T		Neurodevelopmental delay	Likely pathogenic (-)
X-49191698-G-T			Benign (Dec 31, 2019)
X-49191725-G-T		Intellectual disability, X-linked 96	Uncertain significance (Apr 12, 2023)
X-49191730-C-G		Intellectual disability, X-linked 96	Pathogenic (May 01, 2009)
X-49191753-A-C			Uncertain significance (May 02, 2022)
X-49191755-G-A			Likely benign (Aug 01, 2021)
X-49193270-A-G		Intellectual disability, X-linked 96	Likely pathogenic (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SYP	protein_coding	protein_coding	ENST00000263233	6	12450

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.915	0.0844	121170	1	0	121171	0.00000413

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.33	87	130	0.670	0.00000990	2019
Missense in Polyphen		19	52.4	0.36259		874
Synonymous	-1.09	71	60.3	1.18	0.00000508	633
Loss of Function	2.99	1	12.3	0.0811	9.32e-7	168

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	0.0000533	0.0000333
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane. Involved in the regulation of short-term and long-term synaptic plasticity (By similarity). {ECO:0000250}.
• Disease: DISEASE: Mental retardation, X-linked 96 (MRX96) [MIM:300802]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:19377476}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Synaptic Vesicle Pathway (Consensus)

Recessive Scores

• pRec: 0.652

Intolerance Scores

• loftool: 0.0918
• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.392
• hipred: Y
• hipred_score: 0.743
• ghis: 0.569

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.829

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Syp
• Phenotype: normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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)

Gene ontology

• Biological process: endocytosis;synaptic vesicle maturation;regulation of long-term neuronal synaptic plasticity;regulation of short-term neuronal synaptic plasticity;synaptic vesicle endocytosis;synaptic vesicle membrane organization;cellular response to organic substance;regulation of synaptic vesicle exocytosis;regulation of opioid receptor signaling pathway
• Cellular component: synaptic vesicle;cell junction;integral component of synaptic vesicle membrane;neuromuscular junction;presynaptic membrane;neuron projection;terminal bouton;presynaptic active zone;excitatory synapse;Schaffer collateral - CA1 synapse
• Molecular function: cholesterol binding;SH2 domain binding;identical protein binding;protein self-association