MFHAS1

multifunctional ROCO family signaling regulator 1, the group of ROCO family

Basic information

Region (hg38): 8:8783353-8893630

Links

ENSG00000147324 ∙ NCBI:9258 ∙ OMIM:605352 ∙ HGNC:16982 ∙ Uniprot:Q9Y4C4 ∙ 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 MFHAS1 gene.

• Inborn genetic diseases (55 variants)
• not provided (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MFHAS1 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				7	1	8
missense			54	1	1	56
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	54	8	2

Variants in MFHAS1

This is a list of pathogenic ClinVar variants found in the MFHAS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-8797371-C-T		not specified	Uncertain significance (Jan 31, 2024)
8-8797388-C-T		MFHAS1-related disorder	Benign (Nov 20, 2019)
8-8797398-G-A		not specified	Uncertain significance (Jul 21, 2021)
8-8797426-C-T		not specified	Uncertain significance (Oct 27, 2022)
8-8797433-G-C		not specified	Uncertain significance (Aug 22, 2023)
8-8890136-C-T		not specified	Uncertain significance (Feb 28, 2024)
8-8890220-C-G		not specified	Uncertain significance (Mar 08, 2024)
8-8890229-C-T		not specified	Uncertain significance (Apr 26, 2023)
8-8890287-A-G		MFHAS1-related disorder	Likely benign (Apr 26, 2019)
8-8890335-G-C		not specified	Uncertain significance (Apr 25, 2023)
8-8890416-C-A		not specified	Uncertain significance (Jul 25, 2023)
8-8890522-G-C		MFHAS1-related disorder	Likely benign (Jul 06, 2022)
8-8890541-G-C		not specified	Uncertain significance (Apr 04, 2023)
8-8890548-C-T		MFHAS1-related disorder	Likely benign (Jan 01, 2023)
8-8890554-T-A		not specified	Uncertain significance (Jul 14, 2023)
8-8890564-C-T		not specified	Uncertain significance (Jun 29, 2023)
8-8890580-T-A		not specified	Uncertain significance (Feb 13, 2023)
8-8890622-C-A		not specified	Uncertain significance (Jan 11, 2023)
8-8890672-C-G		not specified	Uncertain significance (Jul 11, 2023)
8-8890675-T-A		not specified	Uncertain significance (Feb 10, 2022)
8-8890696-T-C		not specified	Uncertain significance (Nov 09, 2021)
8-8890706-G-A		not specified	Uncertain significance (Feb 28, 2024)
8-8890714-G-A		not specified	Uncertain significance (Jan 03, 2024)
8-8890717-C-A		not specified	Uncertain significance (Jan 08, 2024)
8-8890753-G-A		not specified	Likely benign (Aug 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MFHAS1	protein_coding	protein_coding	ENST00000276282	3	110292

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.24e-9	0.987	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.94	757	621	1.22	0.0000367	6660
Missense in Polyphen		215	225.79	0.95221		2573
Synonymous	-5.73	415	291	1.43	0.0000178	2293
Loss of Function	2.36	19	33.8	0.562	0.00000202	338

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000168	0.000167
Middle Eastern	0.000163	0.000163
South Asian	0.000196	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable GTP-binding protein (PubMed:24286120). Functions in innate immunity and more specifically the inflammatory response as a regulator of the Toll-like receptor TLR2 and TLR4 signaling pathways (PubMed:26599367, PubMed:28471450, PubMed:28609714). Negatively regulates the part of the TLR4 signaling pathway that leads to the activation of the transcription factor AP-1. By retaining the phosphatase complex PP2A into the cytoplasm, prevents the dephosphorylation of the AP- 1 subunit JUN which is required for proper activation of the transcription factor (PubMed:28609714). Both inhibits and activates the TLR2-dependent signaling pathway (PubMed:26599367). Positively regulates the TLR2 signaling pathway to activate specifically the downstream p38 and JNK MAP kinases and promote the polarization of macrophages toward the pro-inflammatory M1 phenotype (PubMed:28471450). It may also play a role in the regulation of inflammation induced by high glucose through the PKB/AKT signaling pathway (PubMed:29168081). Also involved in erythrocyte differentiation through activation of the ERK1/ERK2 signaling pathway (PubMed:23327923). {ECO:0000269|PubMed:23327923, ECO:0000269|PubMed:24286120, ECO:0000269|PubMed:26599367, ECO:0000269|PubMed:28471450, ECO:0000269|PubMed:28609714, ECO:0000269|PubMed:29168081}.
• Disease: DISEASE: Note=A chromosomal aberration involving MFHAS1 may be a cause of B-cell lymphoma. Translocation t(8;14)(p23.1;q21) with a cryptic exon named '14q21 element'. The resulting fusion protein named 'chimeric MASL1' is tumorigenic in nude mice. {ECO:0000269|PubMed:14691450}.

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.509
• rvis_EVS: -1.19
• rvis_percentile_EVS: 5.89

Haploinsufficiency Scores

• pHI: 0.105
• hipred: N
• hipred_score: 0.394
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.410

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mfhas1

Gene ontology

• Biological process: inflammatory response;erythrocyte differentiation;negative regulation of toll-like receptor 2 signaling pathway;positive regulation of toll-like receptor 2 signaling pathway;negative regulation of toll-like receptor 4 signaling pathway;negative regulation of protein dephosphorylation;regulation of macrophage activation;innate immune response;positive regulation of JNK cascade;negative regulation of inflammatory response;positive regulation of protein kinase B signaling;positive regulation of ERK1 and ERK2 cascade;negative regulation of protein localization to nucleus;positive regulation of p38MAPK cascade
• Cellular component: cytoplasm;mitochondrion;lysosome;cytoskeleton
• Molecular function: protein binding;GTP binding;ubiquitin protein ligase binding;protein phosphatase 2A binding