RNF212

protein-coding

ring finger protein 212, the group of Ring finger proteins

Gene summary

This gene encodes a RING finger protein that may function as a ubiquitin ligase. The encoded protein may be involved in meiotic recombination. This gene is located within a linkage disequilibrium block and polymorphisms in this gene may influence recombination rates. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

Previous symbols:

LOC285498

MANE transcript

NM_001131034.4

Inheritance

ClinVar variants

P:1U:42B:8

Top phenotype

Spermatogenic failure 62

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr4:1,056,250-1,113,564

External References & Databases

Ensembl (ENSG00000178222)

Transcript & Mutation Effects

hg38 • Region Span ~57.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 62LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030508

Submitter: Labcorp Genetics (formerly Invitae)

spermatogenic failure 62LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030508

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spermatogenic failure 62AR

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 31125047

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RNF212 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 3

Non-obstructive azoospermiaTotal: 1

Spermatogenic failure 62Total: 1

Breast ductal adenocarcinomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001131034.4. 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	4 clinvar		5
missense			39 clinvar	3 clinvar	1 clinvar	43
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	42	7	1	51

Highest pathogenic variant AF is 0.00016425137

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001131034.4	RefSeq	NP_001124506.1	10	MANE Select
ENST00000433731.7	Ensembl	ENSP00000389709.2	10	MANE Select
NM_001193318.3	RefSeq	NP_001180247.1	4	Standard
NM_001366918.1	RefSeq	NP_001353847.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

meiotic gene conversion
synapsis
reciprocal meiotic recombination
protein sumoylation
chiasma assembly

Molecular Function

SUMO transferase activity
metal ion binding

Cellular Component

synaptonemal complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000433731
Coding exons: 10
Length: 57313
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0706	162	165	0.985	0.00000834	1927
Missense (PolyPhen)		36	40.85	0.88127		491
Synonymous	0.167	64	65.7	0.974	0.00000399	559
Loss of Function	1.95	7	15.2	0.460	6.43e-7	193

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: SUMO E3 ligase that acts as a regulator of crossing-over during meiosis: required to couple chromosome synapsis to the formation of crossover-specific recombination complexes. Localizes to recombination sites and stabilizes meiosis-specific recombination factors, such as MutS-gamma complex proteins (MSH4 and MSH5) and TEX11. May mediate sumoylation of target proteins MSH4 and/or MSH5, leading to enhance their binding to recombination sites. Acts as a limiting factor for crossover designation and/or reinforcement and plays an antagonist role with CCNB1IP1/HEI10 in the regulation of meiotic recombination (By similarity). {ECO:0000250}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0958

Gene Damage Prediction

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