FRYL

protein-coding

FRY like transcription coactivator, the group of Armadillo like helical domain containing

Gene summary

Predicted to be involved in cell morphogenesis and neuron projection development. Predicted to be active in cell cortex and site of polarized growth. Implicated in Pan-Chung-Bellen syndrome. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

KIAA0826

MANE transcript

NM_015030.2

Inheritance

ClinVar variants

P:32U:422B:35

Top phenotype

Pan-Chung-Bellen syndrome

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr4:48,497,357-48,780,322

External References & Databases

Ensembl (ENSG00000075539)

Transcript & Mutation Effects

hg38 • Region Span ~283.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Pan-Chung-Bellen syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0975953

Submitter: PanelApp Australia

Pan-Chung-Bellen syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0975953

Submitter: G2P

complex neurodevelopmental disorderDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Pan-Chung-Bellen syndromeAD

Manifestation: Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 38479391

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FRYL variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 300

not providedTotal: 146

Pan-Chung-Bellen syndromeTotal: 31

FRYL-related developmental disorderTotal: 15

FRYL-related disorderTotal: 4

See casesTotal: 1

FRYL-associated neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015030.2. 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			7 clinvar	7 clinvar	3 clinvar	17
missense			368 clinvar	20 clinvar	4 clinvar	392
nonsense	3 clinvar	5 clinvar	13 clinvar			21
start loss			1 clinvar			1
frameshift	5 clinvar	14 clinvar	19 clinvar			38
splice donor/acceptor (+/-2bp)		5 clinvar	14 clinvar	1 clinvar		20
Total	8	24	422	28	7	489

Highest pathogenic variant AF is 0.0000020563832

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015030.2	RefSeq	NP_055845.1	61	MANE Select
ENST00000358350.9	Ensembl	ENSP00000351113.4	61	MANE Select
ENST00000503238.6	Ensembl	ENSP00000426064.2	30	Standard
ENST00000505759.1	Ensembl	ENSP00000422988.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fryl	Danio rerio	Structure: head Quality: malformed abnormal

Gene / Model

Organism

Observed Phenotype

fryl

Danio rerio

Structure: head

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell morphogenesis
neuron projection development

Cellular Component

cell cortex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358350
Coding exons: 61
Length: 282962
Individuals with no LoFs: 124753
Homozygous LoFs: 0
Heterozygous LoFs: 43
Defined: 124796
p: 0.000172

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.96	1236	1.57e+3	0.790	0.0000812	19861
Missense (PolyPhen)		487	716.58	0.67962		9251
Synonymous	2.09	498	561	0.888	0.0000298	5690
Loss of Function	9.19	31	154	0.201	0.00000847	1906

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00020	0.00019	rare
Latino/Admixed American	0.00034	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00029	0.00028	rare
Finnish	0.000094	0.000093	rare
European (Non-Finnish)	0.00018	0.00017	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a key role in maintaining the integrity of polarized cell extensions during morphogenesis, regulates the actin cytoskeleton and plays a key role in patterning sensory neuron dendritic fields by promoting avoidance between homologous dendrites as well as by limiting dendritic branching (By similarity). May function as a transcriptional activator. {ECO:0000250, ECO:0000269|PubMed:16061630}.;

Intolerance Scores

LoFtool: 0.529
RVIS EVS: -2.42
RVIS percentile EVS: 1.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: E
Indispensability score: 0.892

Gene Damage Prediction

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