DVL3

dishevelled segment polarity protein 3, the group of Dishevelled segment polarity proteins|PDZ domain containing

Basic information

Region (hg38): 3:184155377-184173614

Links

ENSG00000161202 ∙ NCBI:1857 ∙ OMIM:601368 ∙ HGNC:3087 ∙ Uniprot:Q92997 ∙ 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 3 (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 3	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; Genitourinary	26924530

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DVL3 gene.

• Autosomal dominant Robinow syndrome 3 (6 variants)
• Autosomal dominant Robinow syndrome 1 (5 variants)
• Autosomal dominant Robinow syndrome 2 (4 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DVL3 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	76	5	82
missense			116	17	12	145
nonsense		1		1		2
start loss			1			1
frameshift	6	3	6	1		16
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)	2	1	2			5
splice region				5	9	14
non coding			2	23	9	34
Total	8	5	132	119	26

Variants in DVL3

This is a list of pathogenic ClinVar variants found in the DVL3 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-184155630-A-G			Uncertain significance (Jul 01, 2022)
3-184155637-T-TG			Uncertain significance (May 06, 2024)
3-184155638-G-T			Uncertain significance (Mar 18, 2023)
3-184155640-G-C			Uncertain significance (Oct 05, 2023)
3-184155641-C-G			Likely benign (Jun 12, 2023)
3-184155641-C-T			Likely benign (Mar 18, 2023)
3-184155662-C-T			Likely benign (Aug 10, 2023)
3-184155676-A-G		Inborn genetic diseases	Uncertain significance (Mar 24, 2023)
3-184155689-T-C			Likely benign (Nov 29, 2022)
3-184155701-C-T			Likely benign (Aug 30, 2022)
3-184155715-G-T			Likely benign (Aug 04, 2023)
3-184155729-G-A			Uncertain significance (Oct 26, 2022)
3-184155755-C-T			Likely benign (Sep 19, 2021)
3-184155757-G-A			Uncertain significance (Sep 05, 2023)
3-184155780-A-G			Uncertain significance (Jun 04, 2022)
3-184155787-A-G			Uncertain significance (Jul 16, 2023)
3-184155788-C-T		DVL3-related disorder	Likely benign (Mar 12, 2023)
3-184155963-C-T			Benign (Nov 16, 2018)
3-184163446-G-A			Benign (Dec 01, 2018)
3-184163454-A-G			Likely benign (Sep 13, 2019)
3-184163640-T-A			Likely benign (Oct 03, 2021)
3-184163641-C-G			Likely benign (Oct 03, 2023)
3-184163659-T-C			Likely benign (Aug 23, 2022)
3-184163666-G-A			Likely benign (Apr 12, 2021)
3-184163677-C-T			Uncertain significance (Dec 27, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DVL3	protein_coding	protein_coding	ENST00000313143	15	18223

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.385	0.615	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.32	345	489	0.705	0.0000325	4683
Missense in Polyphen		97	180.18	0.53835		1755
Synonymous	0.596	189	200	0.946	0.0000142	1440
Loss of Function	4.01	7	31.2	0.225	0.00000159	345

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000117	0.000117
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the signal transduction pathway mediated by multiple Wnt genes. {ECO:0000250|UniProtKB:Q61062}.
• Disease: DISEASE: Robinow syndrome, autosomal dominant 3 (DRS3) [MIM:616894]: A form of Robinow syndrome, a rare skeletal dysplasia syndrome characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, genital hypoplasia, renal anomalies, and costovertebral segmentation defects. {ECO:0000269|PubMed:26924530}. 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);EGF-Core;WNT-Core;Neural Crest Differentiation;Notch Signaling Pathway;Wnt Signaling Pathway;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;RHO GTPases Activate Formins;Disassembly of the destruction complex and recruitment of AXIN to the membrane;RHO GTPase Effectors;Signaling by Rho GTPases;PCP/CE pathway;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;Regulation of nuclear beta catenin signaling and target gene transcription;Degradation of beta catenin;TCF dependent signaling in response to WNT;Canonical Wnt signaling pathway;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.177

Intolerance Scores

• loftool: 0.282
• rvis_EVS: -0.96
• rvis_percentile_EVS: 9.17

Haploinsufficiency Scores

• pHI: 0.632
• hipred: Y
• hipred_score: 0.825
• ghis: 0.629

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dvl3
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; vision/eye phenotype; hematopoietic system 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); 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); embryo phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; renal/urinary system 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); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: positive regulation of protein phosphorylation;intracellular signal transduction;non-canonical Wnt signaling pathway;non-canonical Wnt signaling pathway via JNK cascade;positive regulation of JUN kinase activity;positive regulation of GTPase activity;positive regulation of transcription, DNA-templated;protein stabilization;canonical Wnt signaling pathway;Wnt signaling pathway, planar cell polarity pathway;negative regulation of canonical Wnt signaling pathway;planar cell polarity pathway involved in neural tube closure;positive regulation of neuron projection arborization;regulation of cellular protein localization;beta-catenin destruction complex disassembly
• Cellular component: nuclear chromatin;cytosol
• Molecular function: protease binding;signaling receptor binding;frizzled binding;protein binding;beta-catenin binding;protein heterodimerization activity;Rac GTPase binding