XAF1

XIAP associated factor 1, the group of Zinc fingers TRAF-type

Basic information

Region (hg38): 17:6755446-6775647

Links

ENSG00000132530 ∙ NCBI:54739 ∙ OMIM:606717 ∙ HGNC:30932 ∙ Uniprot:Q6GPH4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XAF1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XAF1 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						0
missense			17	2	1	20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	2	1

Variants in XAF1

This is a list of pathogenic ClinVar variants found in the XAF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-6756086-G-C		not specified	Uncertain significance (Jan 09, 2024)
17-6756089-A-C		not specified	Likely benign (Aug 09, 2021)
17-6758118-C-G		not specified	Uncertain significance (Sep 15, 2021)
17-6758142-G-A		not specified	Uncertain significance (Apr 12, 2023)
17-6758192-A-G		not specified	Uncertain significance (Jan 26, 2023)
17-6758221-G-C		not specified	Uncertain significance (Dec 21, 2022)
17-6759688-C-G		not specified	Uncertain significance (Jul 30, 2023)
17-6760434-A-G			Benign (Apr 30, 2020)
17-6760443-T-C		not specified	Uncertain significance (Apr 12, 2022)
17-6760484-G-A		not specified	Uncertain significance (Nov 10, 2022)
17-6760539-T-C		not specified	Uncertain significance (Sep 29, 2023)
17-6760541-C-T		not specified	Uncertain significance (Dec 13, 2022)
17-6760544-C-T		not specified	Uncertain significance (Aug 16, 2022)
17-6760568-G-A		not specified	Uncertain significance (Oct 20, 2021)
17-6770653-G-T		not specified	Uncertain significance (May 30, 2024)
17-6770679-T-G		not specified	Uncertain significance (Nov 08, 2022)
17-6770699-A-T		not specified	Uncertain significance (Jul 26, 2022)
17-6770767-G-A		not specified	Uncertain significance (Sep 17, 2021)
17-6770833-G-A		not specified	Uncertain significance (Jul 27, 2022)
17-6770952-C-A		not specified	Uncertain significance (Feb 15, 2023)
17-6773122-C-T		not specified	Likely benign (Sep 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XAF1	protein_coding	protein_coding	ENST00000361842	7	20201

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.82e-12	0.0185	125703	0	44	125747	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.106	161	165	0.977	0.00000866	1990
Missense in Polyphen		28	36.765	0.7616		442
Synonymous	-0.489	64	59.2	1.08	0.00000321	521
Loss of Function	-0.491	16	14.0	1.14	5.87e-7	191

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000268	0.000268
Ashkenazi Jewish	0.00	0.00
East Asian	0.000549	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000161	0.000158
Middle Eastern	0.000549	0.000544
South Asian	0.000206	0.000196
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Seems to function as a negative regulator of members of the IAP (inhibitor of apoptosis protein) family. Inhibits anti- caspase activity of BIRC4. Induces cleavage and inactivation of BIRC4 independent of caspase activation. Mediates TNF-alpha- induced apoptosis and is involved in apoptosis in trophoblast cells. May inhibit BIRC4 indirectly by activating the mitochondrial apoptosis pathway. After translocation to mitochondria, promotes translocation of BAX to mitochondria and cytochrome c release from mitochondria. Seems to promote the redistribution of BIRC4 from the cytoplasm to the nucleus, probably independent of BIRC4 inactivation which seems to occur in the cytoplasm. The BIRC4-XAF1 complex mediates down-regulation of BIRC5/survivin; the process requires the E3 ligase activity of BIRC4. Seems to be involved in cellular sensitivity to the proapoptotic actions of TRAIL. May be a tumor suppressor by mediating apoptosis resistance of cancer cells. {ECO:0000269|PubMed:11175744, ECO:0000269|PubMed:12029096, ECO:0000269|PubMed:16432762, ECO:0000269|PubMed:17329253, ECO:0000269|PubMed:17613533}.
• Pathway: Copper homeostasis;Cytokine Signaling in Immune system;Immune System;Interferon alpha/beta signaling;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.0853

Intolerance Scores

• loftool: 0.923
• rvis_EVS: 1
• rvis_percentile_EVS: 90.62

Haploinsufficiency Scores

• pHI: 0.0576
• hipred: N
• hipred_score: 0.352
• ghis: 0.399

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0497

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xaf1

Gene ontology

• Biological process: apoptotic process;response to interferon-beta;type I interferon signaling pathway
• Cellular component: nucleus;mitochondrion;cytosol
• Molecular function: zinc ion binding