DVL1

dishevelled segment polarity protein 1, the group of Dishevelled segment polarity proteins|MicroRNA protein coding host genes|PDZ domain containing

Basic information

Region (hg38): 1:1335275-1349418

Links

ENSG00000107404 ∙ NCBI:1855 ∙ OMIM:601365 ∙ HGNC:3084 ∙ Uniprot:O14640 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant Robinow syndrome 2 (Definitive), mode of inheritance: AD
• autosomal dominant Robinow syndrome 2 (Strong), mode of inheritance: AD
• autosomal dominant Robinow syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Robinow syndrome, autosomal dominant 2	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	Audiologic/Otolaryngologic; Craniofacial; Dental; Genitourinary; Musculoskeletal	10319206; 22431878; 25045061; 25817014; 25817016

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DVL1 gene.

• not provided (473 variants)
• Inborn genetic diseases (49 variants)
• Autosomal dominant Robinow syndrome 2 (32 variants)
• Autosomal dominant Robinow syndrome 1 (4 variants)
• DVL1-related condition (4 variants)
• not specified (3 variants)
• Autosomal dominant Robinow syndrome 2;Autosomal dominant Robinow syndrome 1 (3 variants)
• Autosomal dominant Robinow syndrome 1;Autosomal dominant Robinow syndrome 2 (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 DVL1 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			3	102	18	123
missense			166	43	10	219
nonsense	1		3			4
start loss						0
frameshift	11	7	8			26
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)		1	1			2
splice region			6	14	10	30
non coding			1	66	36	103
Total	12	8	183	212	64

Variants in DVL1

This is a list of pathogenic ClinVar variants found in the DVL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-1336133-C-T		DVL1-related disorder	Likely benign (Jun 19, 2019)
1-1336134-GCCACGAGTCACATGATGT-G		Autosomal dominant Robinow syndrome 1	Uncertain significance (Sep 23, 2019)
1-1336146-A-G			Uncertain significance (Jul 19, 2023)
1-1336156-C-T			Uncertain significance (Jan 31, 2024)
1-1336157-G-A			Likely benign (Aug 09, 2023)
1-1336160-G-T			Uncertain significance (Aug 29, 2023)
1-1336161-A-T			Uncertain significance (Feb 10, 2023)
1-1336164-T-A			Likely benign (Jan 29, 2024)
1-1336166-G-A			Likely benign (Oct 05, 2023)
1-1336169-G-A			Likely benign (Sep 12, 2017)
1-1336170-G-C			Uncertain significance (Jun 10, 2021)
1-1336171-G-T			Uncertain significance (Jan 16, 2023)
1-1336179-A-G			Uncertain significance (Dec 30, 2022)
1-1336180-T-C		Inborn genetic diseases	Uncertain significance (May 31, 2023)
1-1336183-C-T			Uncertain significance (Jul 13, 2022)
1-1336187-C-T			Likely benign (Mar 29, 2018)
1-1336196-C-A			Uncertain significance (Oct 27, 2022)
1-1336200-C-T			Uncertain significance (Oct 18, 2022)
1-1336201-G-A			Likely benign (Jul 12, 2022)
1-1336212-A-G			Uncertain significance (May 24, 2022)
1-1336215-T-G		Inborn genetic diseases	Uncertain significance (Mar 29, 2022)
1-1336217-C-T			Likely benign (Dec 27, 2022)
1-1336218-G-A		Inborn genetic diseases	Uncertain significance (Sep 11, 2023)
1-1336223-G-A			Likely benign (Oct 05, 2023)
1-1336223-G-C			Likely benign (Sep 16, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DVL1	protein_coding	protein_coding	ENST00000378891	15	14075

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000373	0.998	125432	0	32	125464	0.000128

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.13	554	484	1.14	0.0000357	4314
Missense in Polyphen		149	155.46	0.95847		1148
Synonymous	-4.97	294	204	1.44	0.0000156	1352
Loss of Function	2.69	14	29.9	0.469	0.00000159	315

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000882	0.0000882
Ashkenazi Jewish	0.00	0.00
East Asian	0.000122	0.000109
Finnish	0.000199	0.000185
European (Non-Finnish)	0.000146	0.000132
Middle Eastern	0.000122	0.000109
South Asian	0.000167	0.000163
Other	0.000517	0.000490

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Required for LEF1 activation upon WNT1 and WNT3A signaling. DVL1 and PAK1 form a ternary complex with MUSK which is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ).
• Disease: DISEASE: Robinow syndrome, autosomal dominant 2 (DRS2) [MIM:616331]: A rare skeletal dysplasia syndrome characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, costovertebral segmentation defects, and renal anomalies. {ECO:0000269|PubMed:25817014, ECO:0000269|PubMed:25817016}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gastric cancer - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Breast cancer - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Notch signaling pathway - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);WNT-Core;MicroRNAs in cardiomyocyte hypertrophy;Regulation of Microtubule Cytoskeleton;Neural Crest Differentiation;Adipogenesis;Notch Signaling Pathway;Hair Follicle Development- Induction (Part 1 of 3);Wnt Signaling Pathway;Association Between Physico-Chemical Features and Toxicity Associated Pathways;ESC Pluripotency Pathways;Wnt Signaling Pathway and Pluripotency;Wnt Signaling in Kidney Disease;Notch Signaling Pathway;Wnt Signaling Pathway;DNA Damage Response (only ATM dependent);Signaling by WNT;Signal Transduction;wnt signaling pathway;segmentation clock;multi-step regulation of transcription by pitx2;RHO GTPases Activate Formins;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Disassembly of the destruction complex and recruitment of AXIN to the membrane;RHO GTPase Effectors;Signaling by Rho GTPases;PCP/CE pathway;agrin in postsynaptic differentiation;Beta-catenin independent WNT signaling;Noncanonical Wnt signaling pathway;Negative regulation of TCF-dependent signaling by DVL-interacting proteins;Degradation of DVL;Wnt;Wnt Canonical;WNT mediated activation of DVL;Degradation of beta catenin;TCF dependent signaling in response to WNT;Canonical Wnt signaling pathway;Wnt Mammals;Presenilin action in Notch and Wnt signaling (Consensus)

Intolerance Scores

• loftool: 0.430
• rvis_EVS: -1.17
• rvis_percentile_EVS: 6.06

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.693
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dvl1
• Phenotype: hearing/vestibular/ear 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); skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of neurotransmitter levels;positive regulation of protein phosphorylation;transcription by RNA polymerase II;negative regulation of protein kinase activity;neurotransmitter secretion;axon guidance;neuromuscular junction development;neural tube development;convergent extension involved in neural plate elongation;cytoplasmic microtubule organization;negative regulation of protein binding;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;protein localization to nucleus;social behavior;protein localization to microtubule;intracellular signal transduction;non-canonical Wnt signaling pathway;receptor clustering;positive regulation of transcription, DNA-templated;collateral sprouting;axon extension;dendrite morphogenesis;synapse organization;protein stabilization;canonical Wnt signaling pathway;Wnt signaling pathway, planar cell polarity pathway;prepulse inhibition;dendritic spine morphogenesis;skeletal muscle acetylcholine-gated channel clustering;negative regulation of canonical Wnt signaling pathway;cochlea morphogenesis;planar cell polarity pathway involved in neural tube closure;presynapse assembly;positive regulation of neuron projection arborization;regulation of cellular protein localization;beta-catenin destruction complex disassembly;positive regulation of protein localization to presynapse;regulation of synaptic vesicle exocytosis;positive regulation of excitatory postsynaptic potential
• Cellular component: cytosol;microtubule;postsynaptic density;lateral plasma membrane;clathrin-coated vesicle;growth cone;cytoplasmic vesicle;neuron projection;neuronal cell body;dendritic spine;synapse;Schaffer collateral - CA1 synapse;presynapse;glutamatergic synapse;Wnt signalosome
• Molecular function: frizzled binding;protein binding;beta-catenin binding;enzyme binding;protein kinase binding;identical protein binding;Rac GTPase binding