GREB1L

GREB1 like retinoic acid receptor coactivator

Basic information

Region (hg38): 18:21242231-21526112

Previous symbols: [ "KIAA1772" ]

Links

ENSG00000141449 ∙ NCBI:80000 ∙ OMIM:617782 ∙ HGNC:31042 ∙ Uniprot:Q9C091 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• renal hypodysplasia/aplasia 3 (Definitive), mode of inheritance: AD
• renal hypodysplasia/aplasia 3 (Moderate), mode of inheritance: AD
• renal hypodysplasia/aplasia 3 (Limited), mode of inheritance: AD
• renal hypodysplasia/aplasia 3 (Definitive), mode of inheritance: AD
• bilateral renal agenesis (Supportive), mode of inheritance: AR
• renal agenesis, unilateral (Supportive), mode of inheritance: AD
• renal hypodysplasia/aplasia 3 (Strong), mode of inheritance: AD
• hearing loss, autosomal dominant 80 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Renal hypodysplasia/aplasia 3; Deafness, autosomal dominant 80	AD	Audiologic/Otolaryngologic; Renal	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	Audiologic/Otolaryngologic; Renal	28739660; 29100090; 29100091; 29955957; 32585897

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GREB1L gene.

• not provided (121 variants)
• Renal hypodysplasia/aplasia 3 (30 variants)
• GREB1L-related condition (25 variants)
• Mayer-Rokitansky-Kuster-Hauser syndrome;Renal hypodysplasia/aplasia 3 (10 variants)
• Rokitansky sequence (8 variants)
• Mayer-Rokitansky-Küster-Hauser syndrome type 2 (8 variants)
• Hearing loss, autosomal dominant 80 (8 variants)
• Renal agenesis;Anhydramnios (3 variants)
• Scoliosis, isolated, susceptibility to, 1 (2 variants)
• Renal agenesis and hypodysplasia (1 variants)
• not specified (1 variants)
• Short stature (1 variants)
• Congenital anomaly of kidney and urinary tract (1 variants)
• Autosomal dominant nonsyndromic hearing loss (1 variants)
• Renal cortical hyperechogenicity (1 variants)
• Profound hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GREB1L gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	25	7	35
missense	1	6	88	8	9	112
nonsense	3	6				9
start loss						0
frameshift	10	4	1			15
inframe indel			1		2	3
splice donor/acceptor (+/-2bp)	1	2				3
splice region		1	4	3	2	10
non coding		1		7	5	13
Total	15	19	93	40	23

Highest pathogenic variant AF is 0.0000131

Variants in GREB1L

This is a list of pathogenic ClinVar variants found in the GREB1L region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-21383512-G-A		GREB1L-related disorder	Benign (Jul 01, 2019)
18-21383532-A-G			Uncertain significance (Mar 19, 2022)
18-21383538-G-A			Uncertain significance (Nov 13, 2022)
18-21383541-A-C		Male infertility with azoospermia or oligozoospermia due to single gene mutation	Likely pathogenic (Sep 01, 2023)
18-21383555-C-T		Renal agenesis and hypodysplasia	association (Nov 02, 2017)
18-21383592-C-T			Uncertain significance (Jan 13, 2024)
18-21383610-T-G			Uncertain significance (Apr 07, 2022)
18-21383612-G-A			Likely benign (Jan 15, 2024)
18-21383615-C-G			Uncertain significance (Sep 27, 2022)
18-21383629-T-G		Short stature	Likely pathogenic (Nov 18, 2001)
18-21383674-AG-A		Renal hypodysplasia/aplasia 3	Likely pathogenic (Jul 14, 2020)
18-21383675-G-A			Uncertain significance (Jul 14, 2023)
18-21384190-T-C			Likely benign (Aug 04, 2023)
18-21384207-T-C		GREB1L-related disorder	Likely benign (Oct 27, 2023)
18-21384214-C-A		GREB1L-related disorder	Uncertain significance (Sep 08, 2023)
18-21384251-G-A			Uncertain significance (Aug 20, 2022)
18-21384251-G-T		GREB1L-related disorder	Uncertain significance (Oct 25, 2023)
18-21384274-G-A			Uncertain significance (Jul 22, 2022)
18-21384325-G-A		Renal hypodysplasia/aplasia 3;Mayer-Rokitansky-Kuster-Hauser syndrome • GREB1L-related disorder	Conflicting classifications of pathogenicity (Apr 01, 2024)
18-21384345-C-T			Likely benign (Apr 01, 2024)
18-21384359-C-T		Male infertility with azoospermia or oligozoospermia due to single gene mutation	Likely pathogenic (Sep 01, 2023)
18-21384395-C-T		Autosomal dominant nonsyndromic hearing loss • Hearing loss, autosomal dominant 80	Uncertain significance (May 29, 2020)
18-21395403-A-G			Uncertain significance (Nov 10, 2023)
18-21395412-G-A		Renal agenesis and hypodysplasia	association (Nov 02, 2017)
18-21395438-A-C			Uncertain significance (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GREB1L	protein_coding	protein_coding	ENST00000580732	31	283176

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.00e-12	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.37	525	1.00e+3	0.523	0.0000543	12545
Missense in Polyphen		219	458.74	0.47739		5749
Synonymous	3.78	297	392	0.757	0.0000217	3803
Loss of Function	8.30	2	84.2	0.0237	0.00000449	1078

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.248
• ghis: 0.410

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Greb1l
• Phenotype: renal/urinary system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: greb1l
• Affected structure: pronephric proximal straight tubule
• Phenotype tag: abnormal
• Phenotype quality: dilated

Gene ontology

• Biological process: metanephros development;branching involved in ureteric bud morphogenesis;kidney development;cardiac ventricle development;male genitalia development;uterus development;paramesonephric duct development;mesonephric duct development
• Cellular component: integral component of membrane