MMS19

protein-coding

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

Gene summary

Enables nuclear estrogen receptor binding activity and transcription coactivator activity. Involved in protein maturation. Located in cytoplasm; nucleoplasm; and spindle. Part of MMXD complex and cytosolic [4Fe-4S] assembly targeting complex. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

MMS19L

MANE transcript

NM_022362.5

Inheritance

ClinVar variants

U:170B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr10:97,458,324-97,498,794

External References & Databases

Ensembl (ENSG00000155229)

Transcript & Mutation Effects

hg38 • Region Span ~40.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodegenerative diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005559

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MMS19 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 153

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022362.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	2 clinvar		7
missense			156 clinvar	5 clinvar	1 clinvar	162
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	170	7	1	178

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 122 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022362.5	RefSeq	NP_071757.4	31	MANE Select
ENST00000438925.7	Ensembl	ENSP00000412698.2	31	MANE Select
NM_001289403.2	RefSeq	NP_001276332.1	30	Standard
NM_001289404.2	RefSeq	NP_001276333.1	26	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

phosphorelay signal transduction system
DNA metabolic process
DNA repair
nucleotide-excision repair
transcription, DNA-templated

Molecular Function

transcription coactivator activity
protein binding
enzyme binding
receptor signaling complex scaffold activity
estrogen receptor binding

Cellular Component

nucleus
nucleoplasm
transcription factor TFIIH holo complex
cytoplasm
spindle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000438925
Coding exons: 31
Length: 40471
Individuals with no LoFs: 125558
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 125609
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.23	470	551	0.852	0.0000298	6563
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00029	0.00027	rare
South Asian	0.00024	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.683

Gene Damage Prediction

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