CRNKL1

protein-coding

crooked neck pre-mRNA splicing factor 1, the group of Spliceosomal C complex|Spliceosomal B complex|Spliceosomal Bact complex|Spliceosomal P complex

Gene summary

The crooked neck (crn) gene of Drosophila is essential for embryogenesis and is thought to be involved in cell cycle progression and pre-mRNA splicing. A protein encoded by this human locus has been found to localize to pre-mRNA splicing complexes in the nucleus and is necessary for pre-mRNA splicing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2013]

MANE transcript

NM_001278628.2

Inheritance

—

ClinVar variants

P:3U:69B:5

Top phenotype

Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr20:20,034,368-20,056,046

External References & Databases

Ensembl (ENSG00000101343)

Transcript & Mutation Effects

hg38 • Region Span ~21.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CRNKL1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 66

Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasiaTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001278628.2. 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						0
missense	2 clinvar	1 clinvar	63 clinvar	4 clinvar		70
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar	1 clinvar		7
Total	2	1	69	5	0	77

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001278628.2	RefSeq	NP_001265557.1	14	MANE Select
ENST00000536226.2	Ensembl	ENSP00000440733.1	14	MANE Select
NM_001278625.2	RefSeq	NP_001265554.1	15	Standard
NM_001278626.2	RefSeq	NP_001265555.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
Metabolism of RNA
mRNA Splicing - Major Pathway
mRNA Splicing
Processing of Capped Intron-Containing Pre-mRNA

Biological Process

spliceosomal complex assembly
mRNA splicing, via spliceosome

Molecular Function

RNA binding
protein binding

Cellular Component

Prp19 complex
nucleus
nucleoplasm
spliceosomal complex
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377340
Coding exons: 15
Length: 21679
Individuals with no LoFs: 125613
Homozygous LoFs: 0
Heterozygous LoFs: 135
Defined: 125748
p: 0.000537

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.880	420	474	0.886	0.0000259	5565
Missense (PolyPhen)		57	107.1	0.53221		1178
Synonymous	-0.805	187	174	1.08	0.00000932	1546
Loss of Function	4.16	19	51.1	0.372	0.00000293	565

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0063	0.0062	notable
Latino/Admixed American	0.00029	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.000033	0.000033	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in pre-mRNA splicing process. {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12084575, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770}.;

Recessive Scores

pRec: 0.175

Intolerance Scores

LoFtool: 0.509
RVIS EVS: 1.05
RVIS percentile EVS: 91.35

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.0941

Gene Damage Prediction

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