PRR14

protein-coding

proline rich 14

Gene summary

The protein encoded by this gene tethers heterochromatin to the nuclear laminar scaffold by binding heterochromatin protein 1 (HP1) and the nuclear lamina. The tether is broken during mitosis and reforms quickly after mitosis, with the encoded protein first binding HP1 and then attaching to the nuclear lamina. This protein also has been shown to promote MyoD activity and skeletal myogenesis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2016]

MANE transcript

NM_024031.5

Inheritance

—

ClinVar variants

U:89B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr16:30,650,717-30,656,413

External References & Databases

Ensembl (ENSG00000156858)

Transcript & Mutation Effects

hg38 • Region Span ~5.7 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 PRR14 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 87

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024031.5. 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			1 clinvar			1
missense			86 clinvar	4 clinvar		90
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	89	4	0	93

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024031.5	RefSeq	NP_076936.1	11	MANE Select
ENST00000300835.9	Ensembl	ENSP00000300835.4	11	MANE Select
NM_001320464.3	RefSeq	NP_001307393.1	11	Standard
ENST00000542965.2	Ensembl	ENSP00000441641.2	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

muscle organ development

Molecular Function

protein binding

Cellular Component

nuclear lamina
nucleoplasm
chromosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000542965
Coding exons: 11
Length: 5724
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125745
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.784	333	376	0.886	0.0000234	3658
Missense (PolyPhen)		112	141.04	0.79412		1425
Synonymous	0.240	146	150	0.975	0.00000869	1339
Loss of Function	3.69	7	28.1	0.249	0.00000174	267

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions in tethering peripheral heterochromatin to the nuclear lamina during interphase, possibly through the interaction with heterochromatin protein CBX5/HP1 alpha (PubMed:24209742). Might play a role in reattaching heterochromatin to the nuclear lamina at mitotic exit (PubMed:24209742). Promotes myoblast differentiation during skeletal myogenesis, possibly by stimulating transcription factor MyoD activity via binding to CBX5/HP1 alpha (PubMed:25906157). Involved in the positive regulation of the PI3K-Akt-mTOR signaling pathway and in promoting cell proliferation, possibly via binding to GRB2 (PubMed:27041574). {ECO:0000269|PubMed:24209742, ECO:0000269|PubMed:25906157, ECO:0000269|PubMed:27041574}.;

Recessive Scores

pRec: 0.0814

Intolerance Scores

LoFtool: 0.512
RVIS EVS: -0.24
RVIS percentile EVS: 36.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.627

Gene Damage Prediction

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