MMS19

MMS19 homolog, cytosolic iron-sulfur assembly component, the group of Armadillo like helical domain containing|Nucleotide excision repair|Cytosolic iron-sulfur assembly components

Basic information

Region (hg38): 10:97458323-97498794

Previous symbols: [ "MMS19L" ]

Links

ENSG00000155229 ∙ NCBI:64210 ∙ OMIM:614777 ∙ HGNC:13824 ∙ Uniprot:Q96T76 ∙ 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 MMS19 gene.

• Inborn genetic diseases (54 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MMS19 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		1
missense			52	2	1	55
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	52	3	1

Variants in MMS19

This is a list of pathogenic ClinVar variants found in the MMS19 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-97458857-G-A		not specified	Uncertain significance (Nov 18, 2022)
10-97458885-G-A		not specified	Uncertain significance (Sep 14, 2022)
10-97459234-G-A		not specified	Uncertain significance (Aug 12, 2021)
10-97459240-G-A		not specified	Uncertain significance (Nov 17, 2022)
10-97459270-C-T		not specified	Uncertain significance (Dec 08, 2023)
10-97459275-C-T		not specified	Uncertain significance (Jan 20, 2023)
10-97459389-A-C		not specified	Uncertain significance (Jun 07, 2023)
10-97459493-G-C		not specified	Uncertain significance (Jan 23, 2024)
10-97459660-G-A		not specified	Uncertain significance (Dec 19, 2022)
10-97459735-T-G		not specified	Uncertain significance (Aug 11, 2022)
10-97460108-C-T		not specified	Uncertain significance (Jun 11, 2021)
10-97460109-G-A		not specified	Uncertain significance (Feb 15, 2023)
10-97460113-C-G		not specified	Uncertain significance (Jan 17, 2023)
10-97460120-C-T		not specified	Uncertain significance (Oct 30, 2023)
10-97460125-T-A		not specified	Uncertain significance (Jan 06, 2023)
10-97460132-T-G		not specified	Uncertain significance (May 23, 2023)
10-97460136-C-T		not specified	Uncertain significance (Jul 09, 2021)
10-97460142-G-C		not specified	Uncertain significance (Apr 22, 2022)
10-97460199-G-A		not specified	Uncertain significance (Nov 22, 2023)
10-97460697-G-A		not specified	Uncertain significance (Dec 17, 2023)
10-97460966-C-T		not specified	Uncertain significance (Jul 21, 2021)
10-97462067-C-T		not specified	Uncertain significance (Mar 31, 2023)
10-97462069-T-C		not specified	Uncertain significance (May 06, 2022)
10-97462088-G-A		not specified	Uncertain significance (Nov 09, 2021)
10-97462627-G-A			Likely benign (Mar 28, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MMS19	protein_coding	protein_coding	ENST00000438925	31	40471

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00829	0.992	125558	0	51	125609	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.23	470	551	0.852	0.0000298	6563
Missense in Polyphen		82	108.44	0.75619		1253
Synonymous	0.865	204	220	0.926	0.0000112	2115
Loss of Function	4.99	15	54.9	0.273	0.00000270	640

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000253	0.000243
Ashkenazi Jewish	0.0000998	0.0000993
East Asian	0.000221	0.000218
Finnish	0.000141	0.000139
European (Non-Finnish)	0.000288	0.000273
Middle Eastern	0.000221	0.000218
South Asian	0.000238	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins specifically involved in DNA metabolism and genomic integrity. In the CIA complex, MMS19 acts as an adapter between early-acting CIA components and a subset of cellular target iron-sulfur proteins such as ERCC2/XPD, FANCJ and RTEL1, thereby playing a key role in nucleotide excision repair (NER), homologous recombination- mediated double-strand break DNA repair, DNA replication and RNA polymerase II (POL II) transcription (PubMed:22678362, PubMed:22678361, PubMed:29225034, PubMed:23585563). As part of the mitotic spindle-associated MMXD complex, plays a role in chromosome segregation, probably by facilitating iron-sulfur cluster assembly into ERCC2/XPD (PubMed:20797633). Indirectly acts as a transcriptional coactivator of estrogen receptor (ER), via its role in iron-sulfur insertion into some component of the TFIIH-machinery (PubMed:11279242). {ECO:0000269|PubMed:11279242, ECO:0000269|PubMed:20797633, ECO:0000269|PubMed:22678361, ECO:0000269|PubMed:22678362, ECO:0000269|PubMed:23585563, ECO:0000269|PubMed:29225034}.

Intolerance Scores

• loftool: 0.968
• rvis_EVS: -0.01
• rvis_percentile_EVS: 52.35

Haploinsufficiency Scores

• pHI: 0.219
• hipred: Y
• hipred_score: 0.704
• ghis: 0.547

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.683

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mms19

Gene ontology

• Biological process: phosphorelay signal transduction system;DNA metabolic process;DNA repair;nucleotide-excision repair;transcription, DNA-templated;cellular response to DNA damage stimulus;chromosome segregation;response to hormone;iron-sulfur cluster assembly;positive regulation of transcription, DNA-templated;protein maturation by iron-sulfur cluster transfer;positive regulation of double-strand break repair via homologous recombination
• Cellular component: nucleus;nucleoplasm;transcription factor TFIIH holo complex;cytoplasm;spindle;cytosol;membrane;MMXD complex;CIA complex
• Molecular function: transcription coactivator activity;protein binding;enzyme binding;receptor signaling complex scaffold activity;estrogen receptor binding;protein binding, bridging