ANLN

protein-coding

anillin, actin binding protein, the group of Pleckstrin homology domain containing

Gene summary

This gene encodes an actin-binding protein that plays a role in cell growth and migration, and in cytokinesis. The encoded protein is thought to regulate actin cytoskeletal dynamics in podocytes, components of the glomerulus. Mutations in this gene are associated with focal segmental glomerulosclerosis 8. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

MANE transcript

NM_018685.5

Inheritance

ClinVar variants

P:2U:323B:132

Top phenotype

Focal segmental glomerulosclerosis 8

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr7:36,389,821-36,453,791

External References & Databases

Ensembl (ENSG00000011426)

Transcript & Mutation Effects

hg38 • Region Span ~64.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial idiopathic steroid-resistant nephrotic syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019006

Submitter: Orphanet

focal segmental glomerulosclerosis 8MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014462

Submitter: PanelApp Australia

focal segmental glomerulosclerosis 8LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014462

Submitter: Ambry Genetics

focal segmental glomerulosclerosis 8STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014462

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Focal segmental glomerulosclerosis 8AD

Manifestation: Renal

Intervention: Renal

Rationale: The condition can involve renal failure, and early diagnosis may enable management considerations; Renal transplant has been described

Comments: Renal transplant has been described

Refs: 24676636

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ANLN variants in ClinVar

7 Conditions Cataloged

not providedTotal: 424

not specifiedTotal: 179

ANLN-related disorderTotal: 61

Focal segmental glomerulosclerosis 8Total: 46

Nephrotic syndromeTotal: 1

Chronic kidney diseaseTotal: 1

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018685.5. 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			6 clinvar	75 clinvar	8 clinvar	89
missense	1 clinvar	1 clinvar	301 clinvar	46 clinvar	2 clinvar	351
nonsense			8 clinvar			8
start loss			1 clinvar			1
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			4 clinvar	1 clinvar		5
Total	1	1	323	122	10	457

Highest pathogenic variant AF is 0.00003928582

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018685.5	RefSeq	NP_061155.2	24	MANE Select
ENST00000265748.7	Ensembl	ENSP00000265748.2	24	MANE Select
NM_001284301.3	RefSeq	NP_001271230.1	23	Standard
NM_001284302.3	RefSeq	NP_001271231.1	23	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
anln	Danio rerio	Structure: retinal ganglion cell Quality: process quality abnormal

Gene / Model

Organism

Observed Phenotype

anln

Danio rerio

Structure: retinal ganglion cell

Quality: process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Retinoblastoma (RB) in Cancer

Biological Process

mitotic cytokinesis
actomyosin contractile ring assembly
septin ring assembly
hematopoietic progenitor cell differentiation
regulation of exit from mitosis

Molecular Function

actin binding
GTP-Rho binding
cadherin binding

Cellular Component

nucleoplasm
actomyosin contractile ring
actin cytoskeleton
midbody
bleb

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265748
Coding exons: 24
Length: 63986
Individuals with no LoFs: 125680
Homozygous LoFs: 0
Heterozygous LoFs: 68
Defined: 125748
p: 0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.897	531	592	0.896	0.0000317	7329
Missense (PolyPhen)		229	266.12	0.86052		3205
Synonymous	0.241	200	204	0.979	0.0000104	2171
Loss of Function	5.39	14	58.5	0.239	0.00000320	720

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00029	0.00028	rare
South Asian	0.00080	0.00078	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for cytokinesis (PubMed:16040610). Essential for the structural integrity of the cleavage furrow and for completion of cleavage furrow ingression. Plays a role in bleb assembly during metaphase and anaphase of mitosis (PubMed:23870127). May play a significant role in podocyte cell migration (PubMed:24676636). {ECO:0000269|PubMed:10931866, ECO:0000269|PubMed:12479805, ECO:0000269|PubMed:15496454, ECO:0000269|PubMed:16040610, ECO:0000269|PubMed:16357138, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:24676636}.;
Disease: DISEASE: Focal segmental glomerulosclerosis 8 (FSGS8) [MIM:616032]: A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. {ECO:0000269|PubMed:24676636}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.152

Intolerance Scores

LoFtool: 0.758
RVIS EVS: -1.15
RVIS percentile EVS: 6.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.921

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High