RMI2

protein-coding

RecQ mediated genome instability 2

Gene summary

RMI2 is a component of the BLM (RECQL3; MIM 604610) complex, which plays a role in homologous recombination-dependent DNA repair and is essential for genome stability (Xu et al., 2008 [PubMed 18923082]).[supplied by OMIM, Nov 2008]

Previous symbols:

C16orf75

MANE transcript

NM_152308.3

Inheritance

ClinVar variants

U:47B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.31

Max pathogenic AF

—

Genomic locus

chr16:11,249,619-11,381,662

External References & Databases

Ensembl (ENSG00000175643)

Transcript & Mutation Effects

hg38 • Region Span ~132.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Bloom syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0008876

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RMI2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 46

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152308.3. 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			1 clinvar			1
missense			46 clinvar	1 clinvar		47
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	47	1	0	48

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152308.3	RefSeq	NP_689521.1	2	MANE Select
ENST00000312499.6	Ensembl	ENSP00000310356.5	2	MANE Select
ENST00000572173.1	Ensembl	ENSP00000461206.1	2	Standard
ENST00000576027.1	Ensembl	ENSP00000459601.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fanconi anemia pathway - Homo sapiens (human)
HDR through Single Strand Annealing (SSA)
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
DNA Repair
Gene expression (Transcription)

Biological Process

DNA replication
DNA repair
regulation of sister chromatid segregation
negative regulation of double-strand break repair via homologous recombination

Molecular Function

DNA binding
protein binding

Cellular Component

nucleoplasm
cytosol
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000312499
Coding exons: 2
Length: 102144
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.621	45	34.7	1.30	0.00000157	909
Missense (PolyPhen)		14	13.838	1.0117		290
Synonymous	-1.49	19	12.3	1.54	5.85e-7	316
Loss of Function	-0.350	2	1.53	1.31	6.47e-8	41

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates. It is required to regulate sister chromatid segregation and to limit DNA crossover. Essential for the stability, localization, and function of BLM, TOP3A, and complexes containing BLM. In the RMI complex, it is required to target BLM to chromatin and stress-induced nuclear foci and mitotic phosphorylation of BLM. {ECO:0000269|PubMed:18923082, ECO:0000269|PubMed:18923083, ECO:0000269|PubMed:27977684}.;
Disease: DISEASE: Note=A homozygous deletion of RMI2 has been found in a family with a Bloom-like syndrome and is probable responsible for the phenotype. Patients manifest depigmented skin lesions, multiple cafe-au-lait macules, and growth deficiency. Cells from affected individuals show a high rate of sister chromatid exchange and increased chromosomal breaks. {ECO:0000269|PubMed:27977684}.;

Recessive Scores

pRec: 0.114

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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