TRIM71

protein-coding

tripartite motif containing 71, the group of Tripartite motif family|Ring finger proteins

Gene summary

The protein encoded by this gene is an E3 ubiquitin-protein ligase that binds with miRNAs and maintains the growth and upkeep of embryonic stem cells. This gene also is involved in the G1-S phase transition of the cell cycle. [provided by RefSeq, Dec 2015]

MANE transcript

NM_001039111.3

Inheritance

ClinVar variants

P:9U:141B:44

Top phenotype

Hydrocephalus, congenital, 4

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr3:32,817,997-32,897,824

External References & Databases

Ensembl (ENSG00000206557)

Transcript & Mutation Effects

hg38 • Region Span ~79.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hydrocephalus, congenital communicating, 1MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0032862

Submitter: G2P

hydrocephalus, congenital communicating, 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032862

Submitter: Ambry Genetics

hydrocephalus, congenital communicating, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032862

Submitter: Ambry Genetics

hydrocephalus, congenital communicating, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032862

Submitter: Labcorp Genetics (formerly Invitae)

hydrocephalus, congenital communicating, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032862

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Hydrocephalus, congenital, 4AD

Manifestation: Neurologic

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: 29983323

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRIM71 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 118

not providedTotal: 44

TRIM71-related disorderTotal: 25

Hydrocephalus, congenital communicating, 1Total: 18

Non-obstructive azoospermiaTotal: 8

CryptozoospermiaTotal: 3

Congenital hydrocephalusTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001039111.3. 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				32 clinvar	1 clinvar	33
missense	2 clinvar	4 clinvar	138 clinvar	11 clinvar		155
nonsense	1 clinvar					1
start loss						0
frameshift	1 clinvar	1 clinvar	3 clinvar			5
splice donor/acceptor (+/-2bp)						0
Total	4	5	141	43	1	194

Highest pathogenic variant AF is 6.852873e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001039111.3	RefSeq	NP_001034200.1	4	MANE Select
ENST00000383763.6	Ensembl	ENSP00000373272.3	4	MANE Select
ENST00000918245.1	Ensembl	ENSP00000588304.1	4	Standard
ENST00000918245.2	Ensembl	ENSP00000588304.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
trim71	Danio rerio	Structure: post-vent region Quality: sigmoid abnormal

Gene / Model

Organism

Observed Phenotype

trim71

Danio rerio

Structure: post-vent region

Quality: sigmoid

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MicroRNAs in cancer - Homo sapiens (human)
Mesodermal Commitment Pathway
let-7 inhibition of ES cell reprogramming
Immune System
Adaptive Immune System

Biological Process

G1/S transition of mitotic cell cycle
protein polyubiquitination
neural tube closure
fibroblast growth factor receptor signaling pathway
miRNA metabolic process

Molecular Function

ubiquitin-protein transferase activity
protein binding
zinc ion binding
translation repressor activity
miRNA binding

Cellular Component

P-body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000383763
Coding exons: 4
Length: 79809
Individuals with no LoFs: 112519
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 112520
p: 0.00000444

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.28	295	502	0.588	0.0000305	5581
Missense (PolyPhen)		31	158.33	0.1958		1537
Synonymous	-3.53	294	226	1.30	0.0000142	1867
Loss of Function	4.69	1	27.6	0.0363	0.00000164	265

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)	0.000010	0.000010	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that cooperates with the microRNAs (miRNAs) machinery and promotes embryonic stem cells proliferation and maintenance (Probable). Binds to miRNAs and associates with AGO2, participating in post-transcriptional repression of transcripts such as CDKN1A (By similarity). In addition, participates in post-transcriptional mRNA repression in a miRNA independent mechanism (PubMed:23125361). Facilitates the G1-S transition to promote rapid embryonic stem cell self-renewal by repressing CDKN1A expression. Required to maintain proliferation and prevent premature differentiation of neural progenitor cells during early neural development: positively regulates FGF signaling by controlling the stability of SHCBP1 (By similarity). Specific regulator of miRNA biogenesis. Binds to miRNA MIR29A hairpin and postranscriptionally modulates MIR29A levels, which indirectly regulates TET proteins expression (PubMed:28431233). {ECO:0000250|UniProtKB:Q1PSW8, ECO:0000269|PubMed:23125361, ECO:0000269|PubMed:28431233, ECO:0000305|PubMed:24239284}.;

Recessive Scores

pRec: 0.127

Intolerance Scores

LoFtool: 0.00448
RVIS EVS: -1.13
RVIS percentile EVS: 6.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.512

Gene Damage Prediction

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