GeneBe

GREB1L

protein-coding

GREB1 like retinoic acid receptor coactivator

Gene summary

Acts upstream of or within kidney development. Predicted to be located in membrane. Implicated in autosomal dominant nonsyndromic deafness 80 and renal agenesis. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:
  • KIAA1772

MANE transcript

NM_001142966.3

Inheritance

AR, AD

ClinVar variants

P:103U:293B:141

Top phenotype

Renal hypodysplasia/aplasia 3; Deafness, autosomal dominant 80

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chr18:21,242,232-21,526,112

External References & Databases

Ensembl (ENSG00000141449)NCBI Gene (80000)OMIM (617782)HGNC:31042GenCCUniProt (Q9C091)AlphaFoldClinVar (GREB1L)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~283.9 kb
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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

bilateral renal agenesisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015986

Submitter: Orphanet

hearing loss, autosomal dominant 80STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030998

Submitter: PanelApp Australia

renal hypodysplasia/aplasia 3DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0024520

Submitter: G2P

renal agenesis, unilateralSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019636

Submitter: Orphanet

renal hypodysplasia/aplasia 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0024520

Submitter: Ambry Genetics

renal hypodysplasia/aplasia 3MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0024520

Submitter: Ambry Genetics

renal hypodysplasia/aplasia 3DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0024520

Submitter: Illumina

The GREB1L gene is located on chromosome 18 at q11.1-11.2 and encodes the GREB1 like retinoic acid receptor coactivator protein, which is involved with retinoic acid signaling and is essential for early metanephros and genital development. GREB1L was first reported in relation to autosomal dominant renal agenesis and hypodysplasia (RHD) in 2017 (28739660; Brophy et al. 2017). At least seven unique variants including missense and loss-of-function variants have been reported in the literature. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. Variants in this gene have been reported in at least nine probands from three publications (28739660; Brophy et al. 2017; 29100091; Tomasi et al. 2017; 29100090; Sanna-Cherchi et al. 2017). Although segregation was observed in six families, incomplete penetrance was also noted. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease relationship is supported by animal models and expression studies (Tomasi et al. 2017). In summary, GREB1L is definitively associated with autosomal dominant renal agenesis and hypodysplasia (RHD).

renal hypodysplasia/aplasia 3STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024520

Submitter: Labcorp Genetics (formerly Invitae)

renal hypodysplasia/aplasia 3STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024520

Submitter: PanelApp Australia

hearing loss, autosomal dominant 80LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0030998

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Renal hypodysplasia/aplasia 3; Deafness, autosomal dominant 80AD

Manifestation: Audiologic/Otolaryngologic; Renal

Intervention: Audiologic/Otolaryngologic; Renal

Rationale: Individuals with Renal hypodysplasia/aplasia 3 may manifest with subtle findings such as vesicoureteral reflux, and awareness may allow prophylactic measures to preserve renal function; In Deafness, autosomal dominant 80, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 28739660; 29100090; 29100091; 29955957; 32585897Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GREB1L variants in ClinVar

20 Conditions Cataloged
not providedTotal: 376
GREB1L-related disorderTotal: 152
Renal hypodysplasia/aplasia 3Total: 97
not specifiedTotal: 50
Hearing loss, autosomal dominant 80Total: 37
Renal agenesis and hypodysplasiaTotal: 11
Mayer-Rokitansky-Kuster-Hauser syndromeTotal: 11
Mayer Rokitansky Kuster Hauser syndrome type 1Total: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001142966.3. 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.

EffectPLPVUSLBBSum
synonymous
5
clinvar
95
clinvar
7
clinvar
 107
missense
4
clinvar
20
clinvar
279
clinvar
34
clinvar
5
clinvar
 342
nonsense
10
clinvar
14
clinvar
1
clinvar
 25
start loss
0
frameshift
23
clinvar
24
clinvar
5
clinvar
 52
splice donor/acceptor (+/-2bp)
3
clinvar
5
clinvar
3
clinvar
 11
Total406329312912537

Highest pathogenic variant AF is 0.000030307096

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001142966.3RefSeqNP_001136438.131MANE Select
ENST00000424526.7EnsemblENSP00000412060.131MANE Select
NM_001410867.1RefSeqNP_001397796.132Standard
NM_001410868.1RefSeqNP_001397797.130Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
greb1lDanio rerio

Structure: pronephric proximal straight tubule

Quality: dilated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • metanephros development
  • branching involved in ureteric bud morphogenesis
  • kidney development
  • cardiac ventricle development
  • male genitalia development

Cellular Component

  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000580732
Coding exons
31
Length
283176
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense5.375251.00e+30.5230.000054312545
Missense (PolyPhen)219458.740.477395749
Synonymous3.782973920.7570.00002173803
Loss of Function8.30284.20.02370.000004491078

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Plays a major role in early metanephros and genital development. {ECO:0000269|PubMed:29100091}.;

Recessive Scores

pRec
0.102

Intolerance Scores

RVIS EVS
0.87
RVIS percentile EVS
88.8

Essentials

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

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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