DPYSL5

dihydropyrimidinase like 5, the group of M38 metallopeptidases

Basic information

Region (hg38): 2:26847747-26950351

Links

ENSG00000157851 ∙ NCBI:56896 ∙ OMIM:608383 ∙ HGNC:20637 ∙ Uniprot:Q9BPU6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic intellectual disability (Supportive), mode of inheritance: AD
• Ritscher-Schinzel syndrome 4 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ritscher-Schinzel syndrome 4	AD	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; Musculoskeletal; Neurologic	31474318; 33894126

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DPYSL5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPYSL5 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	3	1	5
missense			25	7	1	33
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)				1		1
splice region					1	1
non coding			2			2
Total	0	0	30	11	2

Variants in DPYSL5

This is a list of pathogenic ClinVar variants found in the DPYSL5 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-26848137-G-T		Ritscher-Schinzel syndrome 4	Uncertain significance (Jul 12, 2023)
2-26898499-C-T			Uncertain significance (Sep 26, 2023)
2-26898521-G-A		Inborn genetic diseases	Uncertain significance (Feb 10, 2022)
2-26898526-G-A			Likely benign (Jun 01, 2024)
2-26898557-G-A		Inborn genetic diseases	Uncertain significance (Feb 03, 2022)
2-26898617-C-G		DPYSL5-related disorder	Uncertain significance (Aug 05, 2024)
2-26898620-G-A		Ritscher-Schinzel syndrome 4	Conflicting classifications of pathogenicity (Jul 22, 2021)
2-26898627-T-A			Uncertain significance (Aug 18, 2022)
2-26898638-G-A		Syndrome with a Dandy-Walker malformation as major feature;Ritscher-Schinzel syndrome 1 • Dandy-Walker syndrome • Ritscher-Schinzel syndrome 4	Conflicting classifications of pathogenicity (Jul 22, 2021)
2-26898657-C-G		Ritscher-Schinzel syndrome 4	Uncertain significance (Jul 13, 2023)
2-26898668-C-T		See cases	Uncertain significance (Mar 09, 2022)
2-26898730-G-A			Likely benign (Nov 01, 2023)
2-26924937-C-A		not specified	Uncertain significance (Apr 18, 2023)
2-26924948-C-T		Ritscher-Schinzel syndrome 4	Uncertain significance (Oct 13, 2022)
2-26924957-A-C		Ritscher-Schinzel syndrome 4	Likely pathogenic (-)
2-26924959-G-A		Inborn genetic diseases	Likely benign (Dec 21, 2022)
2-26924972-G-C		Inborn genetic diseases	Uncertain significance (Mar 25, 2024)
2-26924974-C-T			Uncertain significance (May 25, 2021)
2-26924987-AC-A		not specified	Uncertain significance (Jul 23, 2024)
2-26924990-C-G		Inborn genetic diseases	Uncertain significance (Apr 23, 2024)
2-26924993-A-G		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
2-26925010-G-A		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
2-26925020-T-C		Ritscher-Schinzel syndrome 4	Uncertain significance (Feb 03, 2023)
2-26927277-G-A		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
2-26927359-A-G		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPYSL5	protein_coding	protein_coding	ENST00000288699	12	102605

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000939	125730	0	3	125733	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.08	206	374	0.551	0.0000234	3679
Missense in Polyphen		75	178.89	0.41925		1817
Synonymous	0.311	151	156	0.968	0.0000113	1148
Loss of Function	4.76	0	26.3	0.00	0.00000135	294

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)	0.0000353	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have a function in neuronal differentiation and/or axon growth.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;Semaphorin interactions;Axon guidance;CRMPs in Sema3A signaling (Consensus)

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.0105
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.51

Haploinsufficiency Scores

• pHI: 0.709
• hipred: Y
• hipred_score: 0.685
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.264

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dpysl5
• 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)

Gene ontology

• Biological process: signal transduction;nervous system development;axon guidance
• Cellular component: cytosol;dendrite;neuronal cell body
• Molecular function: protein binding;microtubule binding;hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds