DEF6

DEF6 guanine nucleotide exchange factor, the group of Pleckstrin homology domain containing

Basic information

Region (hg38): 6:35297818-35321771

Links

ENSG00000023892 ∙ NCBI:50619 ∙ OMIM:610094 ∙ HGNC:2760 ∙ Uniprot:Q9H4E7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 87 and autoimmunity (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 87 and autoimmunity	AR	Allergy/Immunology/Infectious; Hematologic	The condition can include severe immune dysregulation, with manifestations including frequent infections and hematologic sequelae (eg, anemia), and awareness may allow medical management of these sequelae, such as via IVIG and antibiotics	Allergy/Immunology/Infectious; Hematologic	31308374; 32562707

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DEF6 gene.

• not_provided (318 variants)
• not_specified (59 variants)
• Immunodeficiency_87_and_autoimmunity (6 variants)
• DEF6-related_disorder (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DEF6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022047.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	110	4	115
missense	1		134	8	2	145
nonsense	3		1			4
start loss						0
frameshift	3	1	1			5
splice donor/acceptor (+/-2bp)						0
Total	7	1	137	118	6

Highest pathogenic variant AF is 0.0000065708205

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DEF6	protein_coding	protein_coding	ENST00000316637	11	23954

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00232	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.03	208	372	0.559	0.0000228	4097
Missense in Polyphen		31	88.826	0.349		1015
Synonymous	1.57	128	153	0.838	0.00000860	1197
Loss of Function	4.89	4	35.4	0.113	0.00000186	369

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000907	0.0000907
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which plays a role in the activation of Rho GTPases RAC1, RhoA and CDC42. Can regulate cell morphology in cooperation with activated RAC1. Plays a role in Th2 (T helper cells) development and/or activation, perhaps by interfering with ZAP70 signaling (By similarity). {ECO:0000250, ECO:0000269|PubMed:12651066, ECO:0000269|PubMed:15023524}.
• Pathway: TCR;Regulation of RAC1 activity;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.280
• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.37

Haploinsufficiency Scores

• pHI: 0.552
• hipred: Y
• hipred_score: 0.783
• ghis: 0.490

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.922

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Def6
• 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); immune system phenotype; cellular phenotype; hematopoietic system phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: def6a
• Affected structure: midbrain hindbrain boundary neural keel
• Phenotype tag: abnormal
• Phenotype quality: increased width

Gene ontology

• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;cytoskeleton;plasma membrane;membrane;filopodium;perinuclear region of cytoplasm
• Molecular function: protein binding