RP1 N985Y - GET-Evidence


RP1 N985Y

(RP1 Asn985Tyr)

Short summary

Probably benign. One report linked this variant to high triglycerides, but a later paper found a nearby SNP with similar association and suggests that both findings are caused by linkage to an undiscovered causal variant.

Variant evidence
Computational -1

Polyphen 2 predicts “probably damaging” effect, BLOSUM100 score indicates Asn to Tyr is disruptive.

Functional -
Case/Control 4

Allele frequency of ~20% contradicts any serious pathogenic effect.

See Fujita Y et al. 2003 (12764676).

Familial -
Clinical importance
Severity -
Treatability -
Penetrance -


Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern


Summary of published research, and additional commentary

Based on the finding of Junyent et al. and the lack of a plausible mechanism linking RP1 to this phenotype, this variant is evaluated as nonpathogenic — we assume for now that it was found due to linkage to a different causal variant. (Our preference is to only create evaluations for causal variants, as otherwise a set of linked variants could be associated with a single phenotypic effect.)

Allele frequency

  • T @ chr8:55539395: 34.9% (3751/10758) in EVS
  • T @ chr8:55701947: 28.1% (36/128) in GET-Evidence
  • Frequency shown in summary reports: 34.9% (3751/10758)


Fujita Y, Ezura Y, Emi M, Ono S, Takada D, Takahashi K, Uemura K, Iino Y, Katayama Y, Bujo H, Saito Y. Hypertriglyceridemia associated with amino acid variation Asn985Tyr of the RP1 gene. J Hum Genet. 2003;48(6):305-8. Epub 2003 May 23. PubMed PMID: 12764676.

Individuals were chosen for this study on the basis of having hyperlipidemic risk (T-Chol >= mg/dl, or HDL-C <= mg/dl). How this gene was chosen is unclear. The authors state “In the course of serial investigations of population genetics for hyperlipoproteinemia in a cohort of an area located in east-central Japan, we recognized a correlation between lipoprotein variations and polymorphism of the RP1 locus.” but give no references and so we don’t know how these studies were conducted and how many genes were being examined.

p = 0.0006 for homozygotes vs others having higher triglycerides (40% higher), p=0.04 for lower HDL (12% higher).

Of the 280 individuals homozygous for this variant, approximately half of the individuals (136) presented with hypertriglyceridemia (TG > 150), whereas only a quarter (14) were hypertriglyceridemic among 52 individuals with one or no copies: the authors report this as p = 0.04, but we calculate it as p = 0.004 using two-tailed Fisher’s exact.

Regarding significance: it’s hard to know whether these p-values can be taken at face value, because it’s unclear how the gene was chosen in the first place — whether and how much multiple hypothesis correction needs to occur. To address this, we score this as having three points rather than the four it might merit if no correction need occur.

PMID: 11926512 implies that overall the risk for hypertriglyceridemia (TG > 150) in Japanese is ~5% (9.4% in males, 0.8% in females), so we use 5% to calculate attributable risk of 3.7% (total 8.7%).

Junyent M, Lee YC, Smith CE, Arnett DK, Tsai MY, Kabagambe EK, Straka RJ, Province M, An P, Lai CQ, Parnell LD, Shen J, Borecki I, Ordovas JM. The effect of a novel intergenic polymorphism (rs11774572) on HDL-cholesterol concentrations depends on TaqIB polymorphism in the cholesterol ester transfer protein gene. Nutr Metab Cardiovasc Dis. 2010 Jan;20(1):34-40. Epub 2009 Apr 11. PubMed PMID: 19364639; PubMed Central PMCID: PMC2817943.

This paper found another SNP nearby and a similar association and note the finding of Fujita et al. — they conclude that “the most plausible explanation is that rs11774572 polymorphism may be in linkage disequilibrium with a yet undiscovered functional mutation in the regulatory region of either GATA4 or RP1 genes.”




hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het T @ chr8:55539395


hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het T @ chr8:55539395










hu43860C - CGI sample GS00253-DNA_A01_200_37
hom T @ chr8:55539395


show discussion


We should determine if this variant is het or hom in PGP1.



hu604D39 - CGI sample GS00253-DNA_B02_200_37
het T @ chr8:55539395










huBEDA0B - CGI sample GS00253-DNA_C01_200_37
hom T @ chr8:55539395




GS06985 - var-GS06985-1100-36-ASM
hom T @ chr8:55701948


GS06994 - var-GS06994-1100-36-ASM
hom T @ chr8:55701948


GS07357 - var-GS07357-1100-36-ASM
hom T @ chr8:55701948


GS10851 - var-GS10851-1100-36-ASM
het T @ chr8:55701948


GS12004 - var-GS12004-1100-36-ASM
hom T @ chr8:55701948


GS18508 - var-GS18508-1100-36-ASM
het T @ chr8:55701948


GS18517 - var-GS18517-1100-36-ASM
het T @ chr8:55701948


GS18940 - var-GS18940-1100-36-ASM
het T @ chr8:55701948


GS19025 - var-GS19025-1100-36-ASM
het T @ chr8:55701948


GS19669 - var-GS19669-1100-36-ASM
hom T @ chr8:55701948


GS19701 - var-GS19701-1100-36-ASM
het T @ chr8:55701948


GS19834 - var-GS19834-1100-36-ASM
het T @ chr8:55701948


GS20509 - var-GS20509-1100-36-ASM
het T @ chr8:55701948


GS21767 - var-GS21767-1100-36-ASM
het T @ chr8:55701948


Other external references

  • rs2293869
  • Score: 0.958 (probably damaging)

Other in silico analyses

  • NBLOSUM100 score = 5
  • GET-Evidence autoscore = 4

Edit history

Gene search

"GENE" or "GENE A123C":

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